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1
Gilder, Michael Frederick James. "Molecular investigations in animal models of Huntington's disease." Thesis, University College London (University of London), 1999. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.325046.
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Liu, Chun. "Individual-based models of wood mice in ecotoxicology." Thesis, University of Reading, 2013. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.590671.
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The wood mouse (Apodemus sylvaticus) is a common and widespread species in Europe and therefore often used as a focal species in the risk assessments of pesticides. Recent years have seen a growing interest in the use of ecological models in ecological risk assessments. The purpose of this PhD project was to construct and apply population models of the wood mouse to support risk assessment of pesticides. In the thesis I first reviewed the current practice of risk assessment and the weaknesses and the advantages of ecological models, in particular individual-based models. Following a modelling cycle, the PhD project started with a literature review of the basic ecology of the wood mouse and relevant information for modelling purposes. A conceptual model was then constructed, based on which an individual-based model was developed. The model was fully described and its ecological credibility was evaluated by the "pattern-oriented" validation method. The model was then used to link the spatial choice of wood mice and their potential exposure to pesticide application in the field. Analyses of the model showed that when the population density reached a high level in the off-crop hedgerows, which act as the source habitat for wood mice, the surplus were driven to the crop fields and thus have a high risk of exposure if pesticides are applied. The model was further developed by incorporating a sub module of toxicokinetic processes which represented exposure as internal concentration instead of ingested dose. The interactions between the spatial patterns of foraging provided by the individual-based model and the temporal patterns of absorption and elimination provided by the toxicokinetic model were explored. The combined model showed little further reduction of risk than either of the two models respectively alone. It suggested that such a combined approach is most likely to bring added value when the spatio-temporal patterns of feeding are at the intermediate level, i.e. when mice divide their foraging between exposed crop and unexposed areas. I then used the model to explore the population-level sensitivity in terms of both population size and population growth rate, to detrimental effects on individual-level life-history traits. The results showed the two indices had different sensitivities to changes in life-history traits. Thus, endpoint from the models used in risk assessments should take into account whether the protection goal is to ensure that the population remains stable or that it grows. The overall high level of sensitivity to survival also indicated that protection should be more focused on acute effects than chronic effects. Finally I summarised the major findings in the thesis and discussed the need for future research, as well as the lessons learnt about conventional risk assessment approach and the opportunities ecological modelling brings for a more realistic and ecologically relevant risk assessment for pesticides.
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Ho, Wing-lau, and 何穎流. "Investigating neurodegeneration in the retina of tau P301L mice." Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2012. http://hub.hku.hk/bib/B4833392X.
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Neurodegeneration is a collective term for the progressive loss of structure, function or even death of neurons. This includes diseases like Alzheimer’s disease, frontotemporal dementia, Parkinson’s disease and motor neuron disease. Recent researches have shown great interest in the role of tau proteins, which have versatile functions including microtubule stabilization and signal relay in the central nervous system.
Retina and optic nerve, being part of the central nervous system, can also be affected by similar processes. In neurodegenerative diseases visual disturbances including difficulties in reading and finding object, depth perception, perceiving structure from motion, color recognition and impairment in spatial contrast sensitivity have all been observed. Some of these defects may be attributed to changes at ocular level.
The effect of tau mutation was investigated in this study utilizing a transgenic P301L tau mice model. Morphometric analysis has been utilized to quatify the neurodegenerative changes, including the thickness of inner nuclear layer(INL), density of retinal ganglion cells(RGCs) and size of RGCs. Retinal sections stained by hematoxylin and eosin(H&E) were analyzed. Comparisons were made between the P301L tau mice and the control mice in addition to comparisons between different age groups.
The study found that there was a significant decrease of thickness of INL of P301L tau mice when compared with control mice. The effect was more pronounced in the peripheral area and the effect increased with age. Regarding density of RGCs, P301L tau mice showed a similar age-related decline as control mice. And regarding the size of RGCs, the RGCs from P301L tau mice increased in size with age and the RGCs from control mice decreased in size with age.published_or_final_version
Anatomy
Master
Master of Medical Sciences
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Nguyen, Tam Hong. "Pex13 Mutant Mice as Models for the Peroxisome Biogenesis Disorders." Thesis, Griffith University, 2008. http://hdl.handle.net/10072/366797.
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Zellweger syndrome (ZS) is the most severe form of a spectrum of disorders resulting from mutations in PEX genes, genes that encode proteins necessary for peroxisome biogenesis. Loss of functional peroxiosmes leads to disruption of multiple metabolic pathways involving the peroxisome, including very long chain fatty acid oxidation and plasmalogen and bile acid synthesis. ZS patients exhibit a range of clinical abnormalities, including facial dysmorphism, cataracts, hypotonia, seizures, psychomotor retardation, and hearing impairment. In terms of tissue pathology, there are also wide ranging effects, including neuronal migration defects, hepatomegaly, retinopathy, and renal cysts. Pex13 encodes a peroxisomal membrane protein that is essential for peroxisome biogenesis. Previous work in this laboratory resulted in the generation of a Pex13-null mouse model for the purpose of investigating the pathogenesis of Zellweger syndrome. The work in the first part of this thesis extends these studies and describes the generation and initial characterisation of tissue-specific Pex13 mouse models. These tissue-specific models are expected be useful tools for analysis of the impact of localised, brain- and liver-specific elimination of peroxisomes on the pathogenesis of ZS. In addition, in the second part of the thesis, a separate and novel hypothesis is addressed as an explanation for the molecular pathogenesis of ZS, through investigating the relationship between reduced peroxisome abundance and microtubule-mediated peroxisome trafficking.
Pex13 brain mutant mice were generated by mating the previously generated Pex13-floxed mice with mice expressing Cre recombinase under the control of the neuron-specific rat nestin promoter. Pex13 brain mutant mice displayed growth retardation beginning at day 5 postnatal, with gradual deterioration until death at approximately day 22 postnatal. Other clinical features included contracted postures, under-developed lower body mass, abnormal and unsteady gait, and abnormal motor coordination. In terms of brain metabolic function, these mice exhibited significant defects in plasmalogen synthesis, but, surprisingly, VLCFA levels were similar to those of littermate control mice. Significantly, peroxisome elimination in brain resulted in increased levels of plasmalogen levels in liver of Pex13 brain mutant mice. Consistent with the expected pathology resulting from deficiency of brain peroxisomes, brain mutants exhibited defective neuronal migration characterised by increased cellular density in the intermediate zone of the neocortex. Microarray analysis of total brain RNA from Pex13 brain mutants revealed several functionally-linked pathways associated with the differentially expressed genes, including cell-cell signalling, cell compromise/death, lipid metabolism, cell movement, and serotonin synthesis.Thesis (PhD Doctorate)
Doctor of Philosophy (PhD)
School of Biomolecular and Physical Sciences
Science, Environment, Engineering and Technology
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陳醒覺 and Sing-kwok Chan. "Mouse preproendothelin-1 gene: transgenic mouse models to study tissue-specific and developmental expression andregulation." Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 1998. http://hub.hku.hk/bib/B31236571.
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Chan, Sing-kwok. "Mouse preproendothelin-1 gene : transgenic mouse models to study tissue-specific and developmental expression and regulation /." Hong Kong : University of Hong Kong, 1998. http://sunzi.lib.hku.hk/hkuto/record.jsp?B19737002.
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Lopez-Lastra, Silvia. "Humanized Mice as Models to study Human Innate Immunity and Immunotherapies." Thesis, Université Paris-Saclay (ComUE), 2017. http://www.theses.fr/2017SACLS039/document.
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Les modèles animaux ont largement contribué à notre compréhension de l’immunologie humaine et des mécanismes pathologiques associés au développement des maladies. Cependant, les modèles murins ne permettent pas de reproduire toute la complexité des pathologies humaines. Les souris à système immunitaire humain (HIS), par leur capacité à récapituler l’hématopoïèse humaine et à être infectées par des pathogènes humains, constituent une solution de choix pour combler ce fossé inter-espèce. Après greffe de cellules souches hématopoïétiques humaines, des souris hôtes sévèrement immunodéprimées permettent un haut niveau de développement du système hémato-lymphoïde humain tout au long de leur vie. Cependant, certains types cellulaires, comme les cellules lymphoïdes innées, ne parviennent pas à se différencier et à fonctionner normalement dans les modèles murins HIS actuels. Ici, nous décrivons le développement d’un modèle souris HIS original, nommé BRGSF, montrant une amélioration de la maturation, de la fonction et de l’homéostasie des cellules natural killer (NK) humaines et des autres ILCs. De plus, en récapitulant les différentes étapes du développement des ILCs humaines, ce modèle souris BRGSF nous a permis d’identifier pour la première fois un précurseur d’ILC (ILCP) présent à la fois dans notre modèle HIS ainsi que dans le sang périphérique et plusieurs organes lymphoïdes et non-lymphoïdes humains. Cette population circulante d’ILCPs pourrait constituer un substrat pour la production d’ILCs matures dans les tissus périphériques en réponse à des stress environnementaux, inflammatoires et/ou infectieux. Dans une seconde partie de ce travail de thèse, nous avons utilisé ces souris BRGS afin de tester l’efficacité de deux immunothérapies reposant sur les lymphocytes innés pour le traitement d’un carcinome colorectal exprimant EGFR et muté pour KRAS. La première approche a consisté en la co-administration des cellules NK dérivées de sang de cordon ombilical et d'anticorps monoclonal cetuximab afin de promouvoir le mécanisme de cytotoxicité cellulaire dépendante des anticorps (ADCC) contre la tumeur. La seconde stratégie a reposé sur l’injection de nanobodies VHH combinant l’inhibition de l’EGFR et l’activation spécifique du récepteur Vγ9Vδ2 des cellules T effectrices. Les résultats de cette étude soulignent l’importance des modèles murins HIS pour la compréhension du développement des lymphocytes innés humains et pour mieux les mettre à profit dans les thérapies anti-tumeursAnimal models have extensively contributed to our understanding of human immunobiology and to uncover the underlying pathological mechanisms occurring in the development of the disease. However, mouse models do not always reproduce the genetic complexity inherent in human disease conditions. Human immune system (HIS) mouse models that are susceptible to human pathogens and can recapitulate human hematopoiesis provide one means to bridge the interspecies gap. Severely immunodeficient host mice support life-long, high level human hematolymphoid development after engraftment with human hematopoietic stem cells (HSC). However, the differentiation and function of some blood cell types, including innate lymphoid cells (ILCs), is poorly characterized in current HIS mice. Here we describe the development of a novel HIS mouse model, named BRGSF, which demonstrate enhanced maturation, function and homeostasis of human natural killer (NK) cells and other ILCs. Furthermore, the BRGSF-based HIS mouse model recapitulated the developmental stages of human ILCs. We could identify for the first time an ILC precursor (ILCP) population that is present both in HIS mice and in human peripheral blood as well as in several lymphoid and non-lymphoid human tissues. This circulating human ILCP population may provide a substrate to generate mature ILCs in tissues in response to environmental stressors, inflammation and infection. In a second part of the thesis we used BRGS immunodeficient mice to assess two innate lymphocyte-based immunotherapeutic approaches for treating EGFR-expressing KRAS-mutated colorectal carcinoma in vivo. The first model used a combination of umbilical cord blood (UCB)-derived NK cells and the monoclonal antibody cetuximab to promote antibody dependent cell cytotoxicity (ADCC) against the tumors. In a second model, we evaluated the therapeutic suitability of novel bispecific VHH constructs that combine inhibition of the EGFR with the target-specific activation of effector Vγ9Vδ2-T cells. These studies highlight the utility for HIS-based mouse models to understand human innate lymphocyte development and to harness these potent effectors for anti-tumor therapies
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Hübner, Roland Karl Peter. "Chromosomal and biochemical variation in wild mice from Switzerland : relevance for models of chromosomal evolution in European house mice." Thesis, University of Oxford, 1992. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.316879.
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Thompson, Sally A. "Modulation of glutathione associated with methylmercury exposure in mice /." Thesis, Connect to this title online; UW restricted, 1996. http://hdl.handle.net/1773/8461.
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Buonincontri, Guido. "Advanced MRI for cardiac assessment in mice." Thesis, University of Cambridge, 2014. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.648679.
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Crossan, Gerard. "Modelling Fanconi anaemia in mice : cellular and pathological consequences of Slx4 deficiency." Thesis, University of Cambridge, 2013. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.607674.
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Shen, Jun. "Factors influencing topotecan CNS penetration in mouse models." View the abstract Download the full-text PDF version, 2008. http://etd.utmem.edu/ABSTRACTS/2008-026-Shen-Index.html.
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Thesis (Ph.D.)--University of Tennessee Health Science Center, 2008.Title from title page screen (viewed on Sept. 17, 2008). Research advisor: Clinton Stewart, Pharm.D. Document formatted into pages (xiii, 105 p. : ill.). Vita. Abstract. Includes bibliographical references (p. 80-102).
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Zhang, Xinmei, and 張新梅. "Generation of mouse models to study intracellular transportation in purkinje cells and melanocytes." Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2004. http://hub.hku.hk/bib/B42577779.
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Zhang, Xinmei. "Generation of mouse models to study intracellular transportation in purkinje cells and melanocytes." Click to view the E-thesis via HKUTO, 2004. http://sunzi.lib.hku.hk/hkuto/record/B42577779.
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Chen, Muhan. "Application of transgenic mice models in functional study of two putative oncogenes ALC-1 and EIF5A2 /." Click to view the E-thesis via HKUTO, 2007. http://sunzi.lib.hku.hk/hkuto/record/B38593464.
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Zhou, Shuangcheng, and 周雙宬. "Defects in early B lymphocyte development in Zmpste24⁻′⁻ mice." Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2009. http://hub.hku.hk/bib/B43703641.
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Tan, Ju Chiat Graduate School of Biomedical Engineering Faculty of Engineering UNSW. "Investigation of abnormal cardiac function in murine models of hypocontractility and hypercontractility." Awarded by:University of New South Wales. Graduate School of Biomedical Engineering, 2006. http://handle.unsw.edu.au/1959.4/28879.
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Heart failure has a significant impact on mortality and morbidity. Dilated cardiomyopathy (DCM) is the third most common cause of heart failure and the most common reason for heart transplantation. Familial DCM is known to be caused by mutations in the LMNA gene encoding lamins A and C. New methods to enhance cardiac contractility would be beneficial in the treatment or prevention of heart failure. The focus of this thesis was to evaluate the mechanisms of altered contractility in two mouse models: the LMNA knockout model (homozygous, Lmna-/-; heterozygous, Lmna+/-) generated by targeted deletion of the lmna gene, and the model of enhanced contractility due to cardiac alpha1A-adrenergic receptor (???1A-AR) overexpression (A1A1). Previous studies have found altered nuclear-desmin connections in lamin A/C deficient mice. It was proposed that these alterations result in ???defective force transmission???, which leads to DCM. Studies in this thesis have supported this hypothesis. Studies of isolated single cardiomyocytes from mice aged 4-6 weeks demonstrated abnormal cell morphology and contractile dysfunction in Lmna-/- cardiomyocytes, while Lmna+/- cells showed no overt phenotype. Excitation-contraction coupling experiments and forcecalcium studies in skinned fibers excluded altered calcium kinetics as a primary cause of DCM in this model, but there was evidence of reduced sarcomere numbers and reduced sarcomere lengths as a contributor to reduce force generation in Lmna-/- and Lmna+/- mice. Previous in vivo studies showed that A1A1 mice had enhanced contractility with the absence of hypertrophy. Studies on isolated single cardiomyocytes from A1A1 mice aged 8-12 weeks showed reduced contractility in the absence of ???1A-AR stimulation, but an exaggerated response to ???1A-AR stimulation. In contrast isolated isovolumic Langendorff perfused A1A1 hearts without ???1A-AR stimulation replicated the enhanced contractility observed in vivo. These studies are consistent with down-regulation of contractility due to the hyperactivity of the overexpressed ???1A-AR in vivo, which only becomes evident in isolated cells without ???1A-AR stimulation due to the loss of functional receptor numbers during isolation. Sufficient spontaneously active ???1A-ARs are preserved in the isolated Langendorff heart preparation to ensure maximum contractility driven by increase calcium release.
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Morrison, David 1981. "The use of a synthetic hedgehog agonist in mouse models of chondrodysplasia /." Thesis, McGill University, 2008. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=116082.
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The role of Indian hedgehog (Ihh) signalling in the regulation of endochondral bone formation is well established. Ihh controls the rate of bone growth by negatively regulating differentiation and positively regulating growth plate chondrocyte proliferation. It has been well documented also that mutations resulting in constitutive activation of signalling through FGFR3 in chondrodysplasia, lead to a significant decrease in this important signalling factor accompanied by reduced proliferation of the chondrocytes and a dwarf phenotype.In an attempt to rescue the chondrodysplasia phenotype hedgehog agonist Hh-Ag 1.4 was injected subcutaneously into mice with achondroplasia (ACH) or with severe achondroplasia with developmental delay and acanthosis negricans (SADDAN) with mixed results.
Administration of a hedgehog agonist in SADDAN mice led to a significant up-regulation of both Ptch and Gli1, as measured by quantitative PCR, indicating that Hh-Ag 1.4 does indeed stimulate hedgehog signalling in vivo. Also, in situ hybridization for Ihh seems to show a down regulation of native Ihh expression in pre-hypertrophic chondrocytes, possibly due to the activation of the negative PTHrP feedback loop. In our study, Hh-Ag 1.4 treatment resulted in an increased growth plate length and reduced size of the hypertrophic zone. The cortical bone flanking the growth plate in mice injected with Hh-Ag 1.4 was 2-3 times thicker than in control mice, which may be attributed to the positive effect of increased Ihh signalling in osteoblastogenesis. Contrary to our expectations, there was also a noticeable reduction in chondrocyte proliferation in mice treated with the agonist.
Overall, the effect on the growth of long bones was not beneficial and the treatment with high doses of Hh-Ag 1.4 did not result in an amelioration of the chondrodysplastic phenotype.
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Fischer, Jared Michael. "Mouse Models of Mutation in vivo." University of Cincinnati / OhioLINK, 2008. http://rave.ohiolink.edu/etdc/view?acc_num=ucin1227214862.
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Thomas, Hilary. "A feasibility study of oncogene transgenic mice as therapeutic models in cytokine research." Thesis, University College London (University of London), 1997. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.264165.
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Heimisdóttir, Hrafndís Brá, and Jill Skärby. "Differences in Whisker Movement in Mouse Models of Parkinson's Disease & Healthy Mice." Thesis, KTH, Skolan för elektroteknik och datavetenskap (EECS), 2020. http://urn.kb.se/resolve?urn=urn:nbn:se:kth:diva-280309.
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Analysing differences in whisking movement between Parkinson’s Disease (PD) modeled mice and healthy control mice can help us to better understand active sensing and the sensorimotor system. In this thesis whisking data obtained from de Voogel’s (2020) master thesis was analysed with the goal to identify differences in whisking movement. The data used was multidimensional data of time series, which consisted of whisker angles over time. The methods used for the analysis were Principal Component Analysis and Hidden Markov Model, as well as some simple statistical procedures. There were found to be differences in whisking movement between PD modeled mice and healthy controls. Differences were observed in movement estimates, how independently the animals were able to move their whiskers as well as in activity of whiskers. Movement estimates of single whiskers varied greatly in PD modeled compared to control mice, where movement estimates were more evenly distributed. The PD modeled mice moved their whiskers more at the same time, especially on the right side of the face, compared to the healthy control mice who moved their whiskers more independently from one another. Finally, PD modeled mice were actively whisking less of the time on average compared to healthy control mice. The study showed that there is indeed a difference in whisking movement between PD modeled mice and healthy control mice, as well as that multidimensional data of time series can be used to analyse and identify differences in whisker movement.Att undersöka skillnader i morrhårsrörelser hos musmodeller med Parkinsons sjukdom och friska möss kan hjälpa oss förstå active sensing och det sensomotoriska systemet bättre. I följande studie undersöks data bestående av morrhårsrörelser från de Voogel’s masteruppsats med målet att identifiera skillnader i mörrhårsrörelser mellan musmodeller med Parkinsons sjukdom och friska möss. Datan som använts var multidimensionella tidsserier bestående av morrhårsvinklar över tid. Metoderna som använts för analysen var principalkomponentanalys, Hidden Markov Models samt några enkla statistiska metoder. Skillnader i morrhårsrörelser mellan musmodeller med Parkinsons sjukdom och friska möss upptäcktes vid rörelseuppskattning, hur fritt mössen kunde röra morrhåren oberoende av varandra samt i aktiviteten av mörrhårsrörelser. Rörelseuppskattingen av morrhåren hos musmodellerna med Parkinsons sjukdom varierade mycket jämfört med de friska mössen där rörelseuppskattningen var jämn. Musmodellerna med Parkinsons sjukdom rörde sina morrhår samtidigt mer, speciellt på högra sidan av ansiktet, jämfört med de friska mössen som rörde sina morrhår mer oberoende av varandra. Slutligen rörde musmodellerna med Parkinsons sjukdom morrhåren aktivt en större del av tiden i genomsnitt jämfört med de friska mössen. Studien visar att det finns skillnader i morrhårsrörelser mellan musmodeller med Parkinsons sjukdom och friska möss och att multidimensionell data av tidsserier kan användas för att analysera och upptäcka dem.
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Gadepalli, Venkat Sundar. "ISOLATION AND CHARACTERIZATION OF MULTIPOTENT LUNG STEM CELLS FROM p53 MUTANT MICE MODELS." VCU Scholars Compass, 2014. http://scholarscompass.vcu.edu/etd/3644.
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Recent advances in understanding lung biology have shown evidence for the existence of resident lung stem cells. Independent studies in identifying and characterizing these somatic lung stem cells have shown the potential role of these cells in lung repair and regeneration. Understanding the functional characteristics of these tissue resident stem/progenitor cells has gained much importance with increasing evidence of cancer stem cells, cells in a tumor tissue with stem cell characteristics. Lung cancer is most commonly characterized by loss of p53 function which results in uncontrolled cell divisions. Incidence of p53 point mutations is highest in lung cancer, with a high percentage of missense mutations as a result of tobacco smoking. Certain point mutations in p53 gene results in its oncogenic gain of functions (GOF), with enhanced tumorigenic characteristics beyond the loss of p53 function. However, there are no available data on characterization of lung stem cells carrying GOF mutations and correlating them with those of normal stem cells, in this study, for the first time we show that percentage of Sca-1 expressing subpopulation is significantly higher in the lungs of mice carrying p53 GOF mutations than those in lungs isolated from p53+/+ wild type mice. Further, we successfully established lung cells differentially expressing two cell surface markers, Sca-1 and PDGFR-α, with results demonstrating existence of different subpopulations of cells in the lung. Results from our project demonstrate the importance of p53 GOF mutations as correlated with specific lung cell subpopulations.
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Tai, Kin-ki Emily, and 戴健琦. "Defining the protective role of cathelicidin on ulcerative colitis in mice." Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2007. http://hub.hku.hk/bib/B40203542.
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Chen, Muhan, and 陳牧唅. "Application of transgenic mice models in functional study of two putative oncogenes: ALC-1 and EIF5A2." Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2007. http://hub.hku.hk/bib/B38593464.
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Huang, Hai, and 黃海. "The role of cyclooxygenase gene in liver inflammation using COX-1 knockout mice." Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2006. http://hub.hku.hk/bib/B45010699.
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Anderson, Philip D. "Genetic control of testicular germ cell tumor susceptibility in mice." Case Western Reserve University School of Graduate Studies / OhioLINK, 2009. http://rave.ohiolink.edu/etdc/view?acc_num=case1247182449.
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Graffmo, Karin Sixtensdotter. "Of mice and men : SOD1 associated human amyotrophic lateral sclerosis and transgenic mouse models." Doctoral thesis, Umeå : Univ, 2007. http://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-1376.
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Rittler, Matthew Robert. "Sarcoplasmic Reticulum Calcium Handling in Maturing Skeletal Muscle From Two Models of Dystrophic Mice." Thesis, Virginia Tech, 2002. http://hdl.handle.net/10919/35619.
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Duchenne's muscular dystrophy (DMD) is a debilitating disease that affects approximately 1 in 3500 boys, with many DMD patients dying before the age of 20 due to cardio-respiratory complications. DMD is the result of defects in the gene that encodes dystrophin, an integral muscle membrane protein. Although the genetic defect has been identified, the relation between the absence of expressed dystrophin and the mechanisms leading to its onset are still unclear. One possibility is that disrupted calcium (Ca2+) handling by the sarcoplasmic reticulum (SR) leads to an increased cytosolic Ca2+ concentration that activates proteolytic and apoptotic pathways that initiate muscle fiber death. However, little is known about the role of disrupted SR function in the onset of DMD.
The purpose of this study was to test the hypothesis that altered calcium cycling by the SR could contribute to elevated cytosolic Ca2+ levels in the early stages of DMD, and thereby account for the onset of disease pathogenesis. Rates of SR Ca2+ uptake and release were determined in quadriceps muscles obtained from maturing dystrophic and control mice prior to the overt signs of the disease at ages ~9 and 21 days. In addition, the content of several key Ca2+ handling proteins, including two isoforms of the sarco(endo)plasmic reticulum ATPase pump (SERCA 1 & 2), ryanodine receptor type 1 (RyR1), parvalbumin, and calsequestrin were determined by Western analysis. Two dystrophic mouse models were used, the mdx mouse which lacks dystrophin, and the mdx:utrophin-deficient (mdx:utrn-/-) mouse which also lacks utrophin, a protein homolog of dystrophin.
The rate of SR Ca2+ uptake in quadriceps muscles of mdx/utrn-/- mice aged 21 days was 73.1% and 61.3% higher than age-matched control and mdx muscles, respectively (p < 0.05). There was no difference in SR Ca2+ release rates between the genotypes at either age. There were significant increases in the content of each of the calcium handling proteins with age (p < 0.05), but no significant differences were detected between genotypes at either age. These data demonstrate the Ca2+ release rates of dystrophic SR are not compromised, but suggest the increased uptake rates of mdx:utrn-/- SR may be an adaptation to increased cytosolic calcium levels, and/or be due to changes in intrinsic SERCA function and/or regulation. The role of increased SR Ca2+ uptakes rates in onset of DMD pathogenesis can not be directly determined from the present data; therefore it is suggested that future studies directly assess cytosolic Ca2+ concentration and examine the role of SERCA regulatory proteins in intact fibers obtained from mdx:utrn-/- muscles at age 21 days.
Master of Science
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Meshram, Mallika. "PEX13 Mutant Mice as Models of Zellweger Syndrome Neuropathogenesis and Peroxisomal Matrix Protein Import." Thesis, Griffith University, 2014. http://hdl.handle.net/10072/366010.
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Peroxisomes are essential for the developing brain as the loss of functional peroxisomes leads to mild to severe Peroxisome Biogenesis Disorders (PBD) with significant neurological involvement. Zellweger Syndrome (ZS) represents the most severe form of PBDs resulting from a mutation in PEX genes, including PEX13, which encode peroxins necessary for peroxisome biogenesis. ZS patients exhibit a range of clinical abnormalities including hypotonia, multi-organ failure, abnormal metabolic profile with significant neuropathologies and death within a year after birth. As mutation in Pex13 in humans result in ZS, animal models with ubiquitous and targeted disruption of PEX13 were generated in order to understand the unifying molecular pathogenesis of ZS. PEX13 knockout (KO) and brain specific disruption of PEX13 mice (referred as PEX13 brain mutant) were developed in our laboratory and applied as experimental tools previously and in this thesis, to explore the molecular and cellular basis of ZS neuropathology. The PEX13 KO mice, exhibits severe ZS phenotype which includes hypotonia, neuronal migration defect, impaired fatty acid oxidation and plasmalogen synthesis, and early neonatal death.Thesis (PhD Doctorate)
Doctor of Philosophy (PhD)
School of Biomolecular and Physical Sciences
Science, Environment, Engineering and Technology
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Santos, André Luís Fernandes dos. "Efeitos dos hormônios esteróides na regeneração muscular e no fenótipo distrófico em camundongo modelo para distrofia muscular congênita." Universidade de São Paulo, 2012. http://www.teses.usp.br/teses/disponiveis/87/87131/tde-05022013-092744/.
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A miostatina é um agente regulador negativo do crescimento muscular. Na terapia de suplementação com testosterona observou-se diminuição na expressão da miostatina. Este trabalho tem como objetivo determinar a influência do esteróides anabolizantes na expressão do gene da miostatina em camundongos normais, C57BL e no modelo distrófico Largemyd. Utilizamos a técnica de PCR em tempo real, para determinarmos a expressão relativa dos genes. Os animais tratados apenas com esteróide apresentaram aumento significativo em sua massa corpórea, com melhora de desempenho nas avaliações funcionais no Largemyd. Não foram observadas diferenças significativas na expressão do genes da miostatina no músculo normal e distrófico. Concluímos que o uso do esteróide anabolizante foi benéfico para o aumento na força do modelo Largemyd, mas o aumento de massa corpórea nestes animais, como no camundongo normal, não deveu-se a inibição da expressão da miostatina.Myostatin is a negative regulator agent of muscle growth. In the testosterone supplementation therapy we observed decreased myostatin expression. The aim of this project is to determine the influence of anabolic steroids in the expression of myostatin gene in normal C57BL mice and in the dystrophic model Largemyd. We used the Real Time PCR assay to determine the relative expression of genes. Animals treated only with steroids presented significant increase in body mass and Largemyd showed improvement in the functional evaluations. There werent significant differences in the myostatin gene expression in the normal and dystrophic muscle. We concluded that the use of anabolic steroid was benefic to the increase of the strength in the Largemyd model, but the increase of body mass in these animals, as in the normal mice, is not related to the inhibition of myostatin expression.
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Giblin, Kathryn Anne. "Is epilepsy a preventable disorder? New evidence from animal models." Yale University, 2010. http://ymtdl.med.yale.edu/theses/available/etd-03052010-144943/.
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Epilepsy accounts for 0.5% of the global burden of disease, and primary prevention of epilepsy represents one of the three 2007 NINDS Epilepsy Research Benchmarks. Efforts to understand and intervene in the process of epileptogenesis have yielded fruitful preventative strategies in animal models. This article reviews the current understanding of epileptogenesis, introduces the concept of a "critical period" for epileptogenesis, and examines strategies for epilepsy prevention in animal models of both acquired and genetic epilepsies. As proof of principle, we investigated whether early preventative treatment during epileptogenesis in the WAG/Rij rat model of primary generalized epilepsy would persistently suppress the epilepsy phenotype in adulthood. Oral ethosuximide was given from age p21 to 5 months, covering the established period for epileptogenesis in this model. We then assessed the epilepsy phenotype by performing electroencephpalogram (EEG) recordings at serial time points after treatment cessation and by immunocytochemically measuring the cortical expression of ion channels Nav1.1, Nav1.6, and HCN1, which are dysregulated in epileptic WAG/Rij rats. Treatment both persistently suppressed seizures, even up to 3 months after treatment cessation, and blocked ion channel dysregulation. These findings indicated that treatment during epileptogenesis prevented the development of the epileptic phenotype. Subsequently, we investigated the C3H/HeJ mouse model of genetic epilepsy as a candidate for future studies in preventative treatment during epileptogenesis. Serial EEG recordings were performed from p5 to 3 months of age. We found that C3H/HeJ mice underwent three distinct, stereotyped phases of seizure development, which suggests that this model would be an appropriate candidate for future research on prevention of epileptogenesis.
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Ferrari, Eleonora. "Characterization of mouse models to study the pathogenesis of celiac disease and the role played by the dysregulation of the intestinal microbiota." Doctoral thesis, Università del Piemonte Orientale, 2021. http://hdl.handle.net/11579/127592.
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Celiac disease (CD) is a permanent intolerance to dietary protein, gluten, from wheat rye and barley. It occurs in about 1% worldwide population, in genetically predisposed individuals bearing human leukocyte antigen DQ2/DQ8. Although gut epithelial cell stress and the innate immune activation are responsible for the breaking oral tolerance to gliadin, the gluten component, the exact mechanisms through which gliadin can stimulate CD onset are still unclear. Here I show how is important to identify in vivo preclinical models of CD to study its pathogenesis, at molecular level. The increasing prevalence of positive serological marker of CD in Cystic Fibrosis (CF) affected patients let to the hypothesis of a link between the two disorders. Results from my studies indicate that CFTR is potentially involved in the pathogenesis of CD, with gliadin peptides inhibiting CFTR activity and expression. Today, the only treatment for CD is a long-term gluten-free diet. Several evidences show that an altered composition of the intestinal microbiota could play a key role in the pathogenesis of CD, through the modulation of intestinal permeability and the regulation of the immune system. Indeed, although further studies are still required to unveil the molecular mechanisms, results reported in the present work clearly indicate that rebalancing the gut microbiota composition by probiotics administration might represent a new strategy to treat CD affected patients.
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Clevenger, Amy Christine. "Developing mouse models to understand olfactory deficits in schizophrenia /." Connect to full text via ProQuest. IP filtered, 2005.
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Chan, Kin-wang, and 陳健宏. "Study of the in vivo role of TSPYL2 in transgenic mice." Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2007. http://hub.hku.hk/bib/B38225049.
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Zhang, Xiaohui. "Analysis of nitric oxide generation in various organs of animal models during ischemia-reperfusion /." Hong Kong : University of Hong Kong, 1999. http://sunzi.lib.hku.hk/hkuto/record.jsp?B21185426.
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Tirado, Santiago Giovanni. "The effects of a human b-amyloid gene on learning and memory in transgenic mice /." Thesis, McGill University, 1994. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=68139.
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Brain deposition of the $ beta$-amyloid protein is an early marker of Alzheimer's disease (AD). AD is a neurodegenerative disorder characterized by learning and memory impairments. Here, mice (B6C3, 8 and 20 months old) transgenic for a human $ beta$-amyloid fragment were compared to normal litter mates in spatial and non-spatial learning tasks in the Morris water maze, according to standard procedures. Four measures of learning and performance were analyzed statistically: latency, total distance swam, mean distance to a platform, and number of trials correct in reaching a platform. Transgenic mice were impaired relative to their litter mates in spatial learning and performed better in the non-spatial task than in the spatial task in the first three measures. An age effect for transgenics was observed in the total distance measure. The results suggest that expression of the human $ beta$-amyloid protein may produce a selective learning deficit in mice.
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Xiang, Li. "Metabolomics study of regulatory effects of exercise training on db/db type 2 diabetic mice." HKBU Institutional Repository, 2018. https://repository.hkbu.edu.hk/etd_oa/489.
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Type 2 diabetes mellitus (T2DM) is mainly caused by genetic modifications and inappropriate life styles. The complexity of T2DM has brought us challenges for a comprehensive understanding of altered metabolic pathways that contributing to the development of T2DM. Therefore, a comprehensive metabolic analysis is needed. To date, taking regular exercise is a common and effective therapeutic way known to antagonize the metabolic disorders of T2DM. However, the regulatory effects of exercise on T2DM or T2DM induced complications have not been clearly characterized. Here, we present the effect of physical activity on biochemical changes in diabetic db/db mice in plasma, urine, skeletal muscle and kidney samples. Based on liquid chromatography coupled with high resolution Orbitrap mass spectrometry (LC-MS) and gas chromatography coupled with mass spectrometry (GC-MS), two major approaches, untargeted and targeted metabolomics studies, have been developed to delineate metabolic signatures in various kinds of biofluid and tissue samples. Targeted quantification methods on acylcarnitines and acyl-CoA have been developed. Untargeted metabolomics analysis by GC-MS and LC-MS have also been developed to draw a more comprehensive view of the metabolic changes in response to T2DM and exercise on db/db diabetic mice. The transcript expressions of mRNA in pathways of interest have also been measured to confirm the hypothesis. Firstly, a targeted quantification method of acylcarnitines by using high resolution parallel reaction monitoring (PRM) on LC-MS platform has been developed. A total of 117 acylcarnitines were detected from plasma and urine samples. The application of targeted profiling of acylcarnitines in db/m+ control and db/db diabetic mice indicated incomplete amino acid and fatty acid oxidation in diabetic mice. Interestingly, the reduction of medium odd-numbered chain acylcarnitines in urine samples was firstly observed between db/m+ and db/db mice. The high resolution PRM method makes it possible to monitor the widespread metabolic changes of the acylcarnitines in response to stimuli. Besides, the accurate MS and MS/MS spectra data of the 117 acylcarnitines could be used as mass spectrometric resources for the identification of acylcarnitines. In addition to targeted metabolomics analysis, untargeted metabolomics profiling analysis in plasma samples indicated that db/db diabetic mice may be more susceptible to exercise for energy expenditure. Interestingly, all the results from plasma, skeletal muscle and kidney samples may demonstrate that physical activity could mitigate insulin resistance in T2DM mice through improving fatty acid β-oxidation (FAO) and eliminating overloaded intermediate which contribute to insulin resistance. Specifically, the results from kidney samples demonstrated that exercise exhibit beneficial effect in reducing hyperlipidemia, expression levels of inflammatory markers (TNFα, IL-6 and COX2) and fibrosis markers (Collagen 1), and alleviating diabetic nephropathy (DN) induced mesangial expansion in kidneys of diabetic mice. The results of metabolic changes in kidney of db/db mice revealed that the accumulation of acyl-CoA, phospholipids and hydroxylated acylcarnitines were substantially ameliorated by exercise, and the reduction of important enzymes CTP1α and Acadl in FAO were partially reversed. In addition, branched-chain amino acids (BCAA) metabolism which positively related to inflammation (TNFα) was down-regulated in DN mice by exercise. What’s more, the accumulation of uric acid, which contributes to inflammation and tubulointestitial fibrosis in kidney disease, together with its six precursors have also been substantially reduced. The results in kidney samples demonstrated that in addition to beneficial effect in alleviating lipotoxicity through improving FAO efficiency, exercise also ameliorated diabetic induced inflammation and fibrosis via promoting BCAA catabolism and accelerating the elimination of uric acid. Together, the mass spectrometry-based metabolomics study is a powerful tool to investigate the regulatory effect of exercise on complex metabolic diseases. The results may provide informative insights into the underlying the mechanism of exercise on T2DM and T2DM induced complications.
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Dorr, Anthony David Peter. "Kinetics and roles of individual TNF receptors in models of acute lung injury in mice." Thesis, Imperial College London, 2010. http://hdl.handle.net/10044/1/5876.
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Mechanical ventilation, essential for the support of patients with acute lung injury (ALI), causes exacerbation of the existing pathology, a process termed ventilator-induced lung injury (VILI). The pro-inflammatory cytokine tumour necrosis factor-alpha (TNF) has been consistently implicated in ALI/VILI. TNF activates two receptors, TNFR p55 and p75 that act in opposition during VILI to promote or protect against pulmonary oedema formation, respectively, but the mechanisms underlying this are unknown. Alveolar and plasma soluble TNFR (sTNFR) levels are elevated in ventilated ALI patients and associated with mortality. However, the relevance of these increases is unclear. This project had two main aims: to investigate kinetics and sources of sTNFRs in the alveoli and plasma and investigate mechanisms underlying differential TNFR signalling during VILI, using in vivo mouse models. Investigation of intraalveolar sTNFRs during VILI, and also ALI induced by intratracheal administration of hydrochloric acid or bacterial toxins, showed that intraalveolar sTNFRs are differentially regulated during ALI: VILI/hydrochloric acid induced leakage of sTNFR p55 and p75 from plasma, whereas bacterial toxins induced intraalveolar p75 production. These differences have important implications for TNF signalling and potential use as clinical markers. Investigation of plasma sTNFRs suggests that VILI induces direct production of sTNFRs by the pulmonary vasculature, as opposed to leakage of intraalveolar sTNFRs into the circulation as previously suggested. Development of a flow cytometry technique to study pulmonary TNFR expression was successfully validated using TNFR deficient tissue, but consolidation of data by immunohistochemistry was unsuccessful. Investigation of differential TNFR signalling mechanisms showed that following intratracheal fluid administration, p75 deficient mice exhibit physiological changes consistent with impaired fluid reabsorption, implicating p75 in lung fluid reabsorption during VILI. These data offer new, potentially clinically applicable insights into the involvement of TNFR biology in VILI/ALI and the novel methodologies developed herein constitute useful tools for future research.
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Capurro, V. "NEW PHARMACOLOGICAL TOOLS FOR AUTISM RESEARCH: OXYTOCIN RECEPTOR MUTANT MICE AND ZEBRAFISH AS NEUROBEHAVIOURAL MODELS." Doctoral thesis, Università degli Studi di Milano, 2011. http://hdl.handle.net/2434/150267.
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Autism is a neurodevelopmental disorder which is characterized by severe and pervasive impairment in reciprocal socialization, qualitative impairment in communication and repetitive or stereotyped behaviour associated to resistance to change. Oxytocin (OT) is a peptidic hormone best known for its role in lactation and parturition. Recently, it has been also shown by several studies involving different lines of knock-out mice to play an important role in the central nervous system (CNS) by acting on the regulation of social, emotional, aggressive behaviour and on learning and memory. Furthermore, prosocial effects following OT administration in humans have been shown. The link between OT and autism has already been traced in preliminary clinical studies as autism affected patients received a beneficial outcome from treatment with OT. Pharmacokinetic (very short half-life), pharmacodynamic (unspecific binding to vasopressin (AVP) receptors) properties and the presence of peripheral side effects of OT, though, make this peptide an unsuitable target for a future clinical use. It is important, in this perspective, to characterize specific animal models in order to validate the use of OT analogs with more suitable characteristics for preclinical research.
To this end, a characterization of the behavioural phenotype of OTR knock-out mice (OTR-/-) and heterozygous littermates (OTR+/-) in comparison with their wild type counterparts (OTR+/+) has been carried out. General home cage behaviour, sensory, motor abilities and emotional behaviour were not affected by the altered genotype. Interestingly, both and OTR+/- and OTR-/- mice exhibited a significant social impairment as quantified in both the sociability and social novelty tests. Furthermore, OTR-/- mice displayed much higher levels of aggression when facing a stranger mouse as a higher number of attacks and tail rattlings has been registered in the neutral cage paradigm. Moreover, when tested in the reversal phase of a T-maze task for their cognitive flexibility, OTR-/- showed a profound impairment in responding to the changes applied in their established routine. All in all, the OTR mutant mouse model provides full range autism-related aberrant behaviours, displaying social impairments, altered aggressive behaviour, a strong resistance to change and stereotyped behaviour. Mechanisms underlying the aberrant phenotype revealed by mutant mice were investigated through autoradiographic binding experiments for both OTR and vasopressin 1A receptor (V1aR) distribution. In addition, pharmacological treatments with OT, AVP and V1aR antagonist SR49059 were done. Binding experiments were carried out in specific brain areas known to exert a key role in integrating the processing of olfactory information that is crucial to regulate social and emotional behaviour in rodents. OTR-/- animals displayed an almost undetectable OTR binding in all tested areas. Furthermore, a slight compensatory up-regulation of V1aR in the hippocampus and a significant down-regulation of the V1aR expression in the anterior olfactory nucleus, amygdala, ventral pallidum and lateral septum were found. As for heterozygous mutants their phenotype appeared as halfway between the wild type and knock out counterparts for OTR binding sites and V1aR binding has been subjected to a slight reduction in ventral pallidum and anterior olfactory nucleus only. Hence, the previously mentioned aberrant behavioural phenotype displayed by OTR mutant mice could be due to an altered OT/AVP receptors concentration in crucial brain areas. Interestingly, intracerebroventicular treatment with both OT and AVP (0.5ng/mouse) in mutant mice was able to rescue the impairment shown in all behavioural tasks. Furthermore, pre-treatment with V1aR antagonist SR49059 (0.5 ng/mouse), which per se did not exert any effect, in association with OT, blocked the social, aggressive and cognitive enhancing effects of the neuropeptide. Our results suggest a strong involvement of AVP, alongside OT, and in particular the subtype 1A of the AVP receptor, in the modulation of social abilities and cognitive flexibility of OTR mutant mice.
Finally, as an increasing interest for the use of zebrafish for social behavioural analyses to study the genetic basis of behaviour is rising, we also evaluated zebrafish potential as a screening tool for neuropsychiatric diseases involving deficits in social behaviour. To this end, we analyzed the effect of OT, AVP but most importantly isotocin (ISO) and vasotocin (AVT) (zebrafish homologues of OT and AVP, respectively) using the shoaling preference test as social paradigm. Dose-response parabolic curves were obtained and all neuropeptides showed significant efficacy in enhancing social interaction, suggesting the involvement of the oxytocin/vasopressin systems and their analogs in the modulation of zebrafish social behaviour.
In conclusion, our findings indicate that OTR-/- and in part OTR+/- mice display autistic-like symptoms rescued by administration of AVP and OT to young adult animals. The OTR mutant mouse is thus instrumental to investigate the neurochemical and synaptic abnormalities underlying autistic-like disturbances and to test new strategies of pharmacological intervention. We also suggest the use of zebrafish as an alternative animal model for the study of social behaviour, especially as a screening tool: future studies involving new molecules acting on OT and AVP systems will be carried out, taking advantage of this new promising model.
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Chan, Chu-fung, and 陳柱峰. "Neuroprotective effects of granulocyte-colony stimulating factor in a mice stroke model." Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2007. http://hub.hku.hk/bib/B40687284.
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Fiedler, Alyssa. "Resting and Maximal Metabolic Rates in Wild White-Footed Mice (Peromyscus leucopus)." Thesis, Université d'Ottawa / University of Ottawa, 2019. http://hdl.handle.net/10393/39857.
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Resting metabolic rate (RMR) represents the lowest level of aerobic metabolism in a resting individual. By contrast, maximal metabolic rate (MMR) reflects the upper limit of aerobic metabolism achieved during intensive exercise. As RMR and MMR define the boundaries of the possible levels of metabolism expressed by a normothermic individual, a key question is whether RMR and MMR are correlated. To evaluate the relationship between RMR and MMR, I took repeated paired measurements of RMR and MMR on 165 white-footed mice (Peromyscus leucopus) during the summer of 2018. Repeatability (R±se) was significant for both RMR and MMR (RRMR=0.15±0.07 and RMMR=0.27±0.12). At the residual level (within-individual), RMR and MMR were significantly and positively correlated (re=0.20, 95% confidence intervals: 0.04, 0.34). Such a positive residual correlation could be result of correlated phenotypic plasticity. By contrast, RMR and MMR were significantly and negatively correlated at the among-individual level (rind=-0.87, 95% confidence intervals: -0.99, -0.28). The negative among-individual correlation suggests there are trade-offs between the maintenance and active components of the energy budget (allocation model). Future research should investigate the relationship between RMR and other energetically expensive behaviours and activities to understand how energy is allocated among individuals.
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Araragi, Naozumi [Verfasser], and Klaus-Peter [Akademischer Betreuer] Lesch. "Electrophysiological investigation of two animal models for emotional disorders - serotonin transporter knockout mice and tryptophan hydroxylase 2 knockout mice / Naozumi Araragi. Betreuer: Klaus-Peter Lesch." Würzburg : Universitätsbibliothek der Universität Würzburg, 2013. http://d-nb.info/1042899460/34.
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Ioshimoto, Gabriela Lourençon. "Estudo da eletrorretinografia do camundongo modelo de alzheimer (3xTg-AD)." Universidade de São Paulo, 2011. http://www.teses.usp.br/teses/disponiveis/47/47135/tde-28042011-155725/.
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Objetivo: Avaliar eletrofisiologicamente a função da retina do camundongo modelo de Alzheimer (3xTg-AD) comparando com seu controle (b6;129-PS1) em um estudo longitudinal com seis idades (2, 4, 6, 8, 10 e 12 meses). Métodos: Eletrorretinogramas (ERGs) foram registrados em 44 camundongos 3xTg-AD e em 23 controles, após administrada anestesia. Para o registro foi colocado um eletrodo de lente de contato sobre a córnea, um eletrodo de referência na cabeça e um terra na cauda. Em sessão de 30-40min de duração foram expostos ao seguinte protocolo de estimulação: 1) Adaptação ao escuro seguida de flashes nas intensidades: 0,003; 0,03; 0,3; 3 e 30 cd.s/m2; 2) Estimulação periódica (30 cd.s/m2) nas freqüências de 12, 18, e 30 Hz, sob luz de fundo (30 cd/m2). Resultados: Os ERGs mostraram dois tipos de respostas escotópicas tanto no grupo dos camundongos controles (b6;129- PS1) quanto nos modelos de Alzheimer. 13% dos camundongos controles e 72% dos modelos de AD apresentaram ERGs com potenciais oscilatórios presentes e tempo implícito da onda-b dentro da faixa esperada (45,31 ± 6,74 ms), enquanto no restante dos grupos, o ERG apresentou latência da onda-b muito aumentada (111,73 ± 22,56 ms) e potenciais oscilatórios ausentes. Devido a estes resultados, os grupos controle e experimental foram subdivididos em: b6;129 com OP, b6;129 sem OP; 3xTg-AD com OP e 3xTg-AD sem OP. Também foi incluído um grupo controle adicional constituído por 9 camundongos C57/B6. Comparando os cinco grupos, nenhuma diferença foi encontrada em relação à amplitude e à latência da onda-a. A amplitude da onda-b também foi semelhante para todos, ao contrário da latência para atingir o pico da onda-b dos grupos b6;129 sem OP e 3xTg-AD sem OP, que se apresentou duas vezes maior do que nos grupos com OP. As amplitudes dos cinco potenciais oscilatórios foram medidas individualmente e não mostraram diferenças entre os controles e os 3xTg-AD. Para o estímulo periódico, a amplitude do 1º harmônico dos grupos com OP mostrou clara diferença entre os grupos controle e o 3xTg-AD, tanto em 12 Hz como em 18 Hz. Os resultados dos dois grupos controle b6;129 e C57/B6 mantiveram-se muito próximos. Os grupos sem OP mantiveram-se sempre próximos a 10 V para as três freqüências de estimulação e mostraram atraso na diferença de fase média do 1º harmônico em 18 e 30 Hz, indicando maior lentidão de resposta, quando comparados aos primeiros. Conclusão: O camundongo 3xTg-AD e seu controle (b6;129) apresentam uma variante lenta e sem OPs do ERG escotópico em parte da população. Células bipolares, amácrinas e ganglionares podem estar alteradas nesses subgrupos (b6;129 sem OP e 3xTg-AD sem OP). Os grupos controle e 3xTg-AD com OPs diferiram quanto à amplitude de resposta à estimulação intermitente, diferença essa que implica em menor capacidade de processamento temporal para o modelo de AD. Sugerimos que as células bipolares de cones podem estar alteradas nos modelos de AD devido às amplitudes mais baixas dos 1os harmônicos desse grupoObjective: To evaluate electrophysiologically the function of the retina of the Alzheimer model mouse (3xTg-AD) comparing it with its control (b6;129-PS1) in a longitudinal study at six ages (2, 4, 6, 8, 10 e 12 months) Methods: Electroretinograms (ERGs) were recorded in 44 anesthetized mice 3xTg-AD and in 23 controls, with a contact lens electrode placed on the cornea, a reference electrode on the head and a ground on the tail. During a 30-40min duration session the mice were exposed to the following stimulation protocol: 1) Scotopic response Dark adaptation followed by flashes at the following intensities: 0,003; 0,03; 0,3; 3 e 30 cd.s/m2; 2) Periodic stimulation (30 cd.s/m2) at the temporal frequencies of 12, 18, e 30 Hz, under background light (30 cd/m2). Results: The ERGs showed two types of scotopic responses, which ocurred in both the control mice (b6;129- PS1) and the Alzheimer´s models (3xTg-AD). 13% of the controls and 72% of the Alzheimer´s models mice presented ERGs with oscillatory potentials (OPs) and b-wave implicit times within the expected range (45,31 ± 6,74 ms), while for the other groups the ERG presented a very delayed b-wave latency (111,73 ± 22,56 ms) and absence of OPs. Given these results, the control and experimental groups were subdivided into: b6;129 with OPs, b6;129 without OPs; 3xTg-AD with OPs e 3xTg-AD without OPs. An additional control group with 9 mice C57/B6 was included. Comparing the five groups, no difference was found in a-wave amplitude and latency. The b-wave amplitude also did not differ among the groups, but the latency of the b-wave for the groups b6;129 without OPs and 3xTg-AD without OPs, was twice as long as in the groups with OPs. The amplitudes of the five OPs, measured individually, did not show differences between controls and 3xTg-AD groups. For the periodic stimulation the amplitude of the first harmonic of the Fourier transform of the groups with OPs showed a clear difference between the control and the 3xTg-AD groups, both for the 12 Hz and for the 18 Hz stimuli. The results of the two control groups (b6;129 and C57/B6) were very close. The groups without OPs had responses always close to 10 V for the three frequencies of stimulation and showed phase delay for the first harmonic, indicating response slowing, compared to the other groups. Conclusions: We found that a sub-group of both triple transgenic (3xTg-AD) and control mice (b6;129) manifest strikingly slow scotopic ERGs that lack OPs. We hypothesize that these response feature may reflect alterations in bipolar, amacrine and ganglion cells. The sub-group of triple transgenic and control mice that exhibited OPs differed in their response to flicker. Alzheimer model had significantly lower flicker-response amplitudes than the controls, suggesting impaired retinal temporal processing. We propose that the flicker results are consistent with alteration in cone bipolar cells in the Alzheimer model mice
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Borges, Paulo Alvim. "Padronização do modelo experimental de lesão da medula espinal e avaliação da lesão neurológica em camundongos." Universidade de São Paulo, 2018. http://www.teses.usp.br/teses/disponiveis/5/5140/tde-09042018-102145/.
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INTRODUÇÃO: A lesão da medula espinal é um dos grandes desafios da medicina. Apesar de décadas de pesquisa sobre o assunto, seu tratamento ainda não é satisfatório. A padronização de modelos de lesão da medula espinal permite a reprodutibilidade e a análise dos resultados sendo importante para a pesquisa sobre o tema. OBJETIVO: Validar a padronização de um modelo de lesão da medula espinal e avaliação da lesão neurológica em camundongos. MÉTODOS: Submetemos 30 camundongos BalbC divididos em 4 grupos experimentais e um grupo controle à lesão da medula espinal torácica por queda de peso de diferentes alturas (gerando lesões de graus variados). O grupo controle (SHAM) foi submetido apenas à laminectomia. Os camundongos foram avaliados por seis semanas durante as quais foram aplicadas escalas de avaliação funcional motora. Após seis semanas os animais foram sacrificados para avaliação histológica das medulas espinais lesadas. Os achados foram correlacionados entre si para validar se a lesão foi efetiva e se os grupos diferenciaram-se entre os diferentes graus de lesão. Adicionalmente avaliamos se as escalas utilizadas são aplicáveis e se são fiéis aos achados histológicos. RESULTADOS: Seis dos trinta camundongos do experimentos evoluíram para óbito sendo um do Grupo 3, um do Grupo 4 e quatro do Grupo 5. Um camundongo do Grupo 4 apresentou autofagia. O Grupo 5 foi excluído do experimento por alta mortalidade e perda de dados. Todas as escalas funcionais estudadas foram estatisticamente diferentes entre si e demonstraram evolução durante o experimento. Os achados foram confirmados por histologia e apresentaram uma correlação forte com as escalas BBB e BMS e moderada a forte com a escala MFS. A Escada Horizontal apresentou forte correlação com a degeneração neurológica porém não apresentou correlação com os demais parâmetros histológicos estudados. CONCLUSÃO: O modelo de lesão da medula espinal em camundongos apresentado neste estudo é efetivo, confiável e reprodutível, com exceção da lesão causada por queda de peso (10g) de 50mm de altura, que traz mortalidade inaceitável. Das escalas estudadas, BBB e BMS são as mais confiáveis, enquanto que a Escada Horizontal tem seu uso discutívelINTRODUCTION: Spinal cord lesion is a great medical challenge. Even with many decades of research, no satisfactory treatment is available yet. The standardization of animal experimentation models makes the spinal cord lesion reproducible allowing a reliable analysis of the results. Hence, standardization is a major concern in spinal cord lesion research. OBJECTIVE: To validate the standardization of a spinal cord lesion model with neurologic evaluation using mice. METHODS: Thirty BalbC mice were divided in four experimental groups and one control group and submitted to spinal cord lesion produced by weight drop from different heights (producing different severity lesions). The control group (SHAM) was submitted to laminectomy only. Every mice was followed up for six weeks during which functional motor scales were applied. After six weeks the animals were sacrificed for histological examination. Findings were correlat-ed to confirm if the spinal cord lesion was effective and if the groups were dif-ferent between themselves. Additionally all functional motor scales were corre-lated with the histological findings to confirm if the scales are reliable and truly represented the spinal cord lesion. RESULTS: Six mice died during the experi-mentation period (one mouse from the Group 3, one mouse from the Group 4 and four mice from Group 5). One mouse from Group 4 presented autophagia and was excluded from the experiment. Group 5 was excluded from the exper-iment for high mortality rates and data loss. All functional motor scales applied demonstrated significant results with moderate or strong correlation with the histological findings. The Horizontal Ladder scale had strong correlation with neurologic degeneration but had weak or worse correlation with the rest of the histological parameters studied. CONCLUSION: The spinal cord lesion model using mice presented in this study is reliable and reproducible, excluding the lesion produced by a weight drop (10g) from 50mm, which brings unacceptable mortality rate. Of all fuctional motor scales studied, BBB and BMS scales are the most reliable. The use of the Horizontal Ladder scale, however, must be carefully evaluated
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Kopaniszen, Malgorzata. "Protective effect of green tea polyphenols on dinitrobenzene sulphonicacid (DNBS)-induced colitis in mice." Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2008. http://hub.hku.hk/bib/B40687466.
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McGlade, Jacqueline Patricia. "Suppression of the asthmatic phenotype in mice by UVB irradiation." University of Western Australia. School of Paediatrics and Child Health, 2008. http://theses.library.uwa.edu.au/adt-WU2009.0086.
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Background: Exposure of skin to UVB radiation (290-320 nm) modulates the immune system, with most studies showing a suppression of Th1-driven immune responses. Investigations into the effects of UVB exposure on allergic respiratory responses have been limited. This study investigated the systemic effects of UVB on Th2-associated immune responses using two different murine models of allergic respiratory inflammation. The mechanism of immune regulation was also examined. Methods and Results: Two murine models of asthma were used: the papain model and the ovalbumin (OVA) model using papain and OVA, respectively, as the allergens. In the papain model, C57BL/6, histamine receptor-1 knockout (H1RKO) and histamine receptor-2 knockout (H2RKO) mice were exposed to a single 4 kJ/m2 dose of UVB (twice a minimal oedemal dose) on shaved dorsal skin three days prior to intranasal sensitisation with papain, a cysteine protease homologue of the house dust mite (Dermatophagoides pteronyssinus) allergen Der p 1. Sensitisation and boost each consisted of five daily intranasal doses of 1 µg papain whilst the challenge consisted of three daily intranasal doses of 100 µg papain. Asthmatic symptoms were assessed 24 h after the final challenge dose. H1RKO mice demonstrated enhanced papain-specific inflammatory responses in the lung-draining lymph nodes (LDLNs) whilst the responses of H2RKO mice closely mimicked those of C57BL/6 mice. UVB irradiation three days before sensitisation reduced in vitro papain-specific proliferation of LDLN cells from C57BL/6 and H1RKO mice but not H2RKO mice 24 h after challenge. The regulatory effect of UVB was transferred by adoptive transfer of 5 x 106 unfractionated LDLN cells from UVB-irradiated, papain-sensitised and -challenged C57BL/6 and H1RKO donor mice into naïve recipients of the corresponding strain that were ii subsequently sensitised and challenged with papain. Additionally, UVB exposure suppressed papain-induced IL-5 and IL-10 production in vitro by LDLN cells from H1RKO mice but not from C57BL/6 mice or H2RKO mice. The results of this study demonstrate systemic immunomodulation of responses to intranasally delivered antigen by UVB irradiation and the induction of regulatory cells in the LDLN following UVB exposure. Furthermore, these results implicate a role for the H2R in UVB-induced suppression of antigen-specific responses in the draining lymph nodes.
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Maier, Shannon Marie. "Murine models in the investigation of lupus etiology." Oklahoma City : [s.n.], 2006.
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Awale, Prabha Sumant. "Microglial alterations in valproic acid models of autism." Kent State University / OhioLINK, 2012. http://rave.ohiolink.edu/etdc/view?acc_num=kent1342798851.
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Loiacono, Christina Marie. "Mechanism of herpes simplex virus type 1 latency in transgenic mouse models." MU has, 2002. http://wwwlib.umi.com/cr/mo/fullcit?p3052194.
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Pettersson, Ulrika. "Blood Flow Regulation and Inflammatory Response in Experimental Models of Diabetes." Doctoral thesis, Uppsala universitet, Institutionen för medicinsk cellbiologi, 2012. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-161807.
Full textAbstract:
Type 2 diabetes is caused by defect pancreatic islet β-cells together with peripheral insulin resistance. The disease is often accompanied by obesity with associated low-grade visceral adipose tissue inflammation, which contributes to insulin resistance. As a consequence of, and a possible compensation for the increased insulin demand, blood flow to the pancreatic islets is increased in animal models of diabetes. This increased blood perfusion might with time affect the vascular network as well as β-cells within the islets. This thesis investigates the role of changes of blood perfusion in pancreatic islets and adipose tissues, as well as the recruitment to and composition of leukocyte subpopulations in insulin-sensitive tissues in experimental models of diabetes. Blood flow measurements in islets and adipose tissues of rats and mice were performed using the microsphere technique, while leukocyte recruitment was studied in the mouse cremaster muscle using intravital microscopy. Increased islet blood flow was observed in the GK rat model of type 2 diabetes, which was decreased by acute as well as continuous 2-week inhibition of β3-adrenoceptors without affecting plasma insulin concentrations. Increased inflammatory leukocyte recruitment was observed in both alloxan-induced and high-fat diet-induced diabetes. However, an impaired bacterial clearance was observed in diabetic mice, which was due to impaired phagocytosis. A gender difference was detected in mice fed a high-fat diet, since obese female mice did not show increased levels of pro-inflammatory circulatory markers or inflammatory leukocytes in the adipose tissue. The main effector cell in the adipose tissue inflammation in high-fat-fed male mice seemed to be the pro-inflammatory macrophage. The Treg population in adipose tissue was increased in female mice, but remained unchanged in male mice on high-fat diet. In conclusion, increased islet blood flow in type 2 diabetes could be reversed by β3-adrenoceptor inhibition, which may maintain islet function. The diabetes-associated hyperglycemia activated leukocytes but impaired their phagocytic ability. High-fat-fed female mice showed less peripheral inflammation due to a smaller number of recruited inflammatory macrophages and a high-fat diet-induced Treg population in intra-abdominal adipose tissues.