Dissertations / Theses: 'TRANSGENIC ANIMAL'

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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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Saijo(Kim), Misa. "Generation of transgenic animal model of hyperthyroid Graves' disease." Kyoto University, 2004. http://hdl.handle.net/2433/147457.

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Bando, Mika. "Studies on pathophysiological significance of intraislet ghrelin using transgenic animal model." 京都大学 (Kyoto University), 2014. http://hdl.handle.net/2433/188712.

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Abilgos, Ramos Riza. "Folate profiling in wild and transgenic rice." Thesis, University of Nottingham, 2010. http://eprints.nottingham.ac.uk/12870/.

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Quantitative profiling of mono- and polyglutamyl folates in rice was achieved using the microbiological assay (MA) and a newly developed liquid chromatography tandem mass spectrometry (LC-MS/MS) method. MA was used to screen 51 rice cultivars for their total folate content and LC-MS/MS was employed to measure naturally occurring mono- and polyglutamated forms of the vitamin in wild type, FPGS Os03g02030 knockout and transgenic lines with overexpressed FPGS genes and with folate binding protein from cow’s milk (cFBP) and rat’s liver (GNMT). Natural variation among rice cultivars in terms of total folate content was measured using MA screening and the validated LC-MS/MS technique of simultaneous profiling of mono- and polyglutamated folates through MeOHAA/PO4 extraction revealed that the naturally-occurring species in wild type rice are 5-CH3-H4PteGlu, 5/10-CHO-H4PteGlu, 5-CH3-H4PteGlu4, 5-CH3-H4PteGlu5 and 5/10-CHO-PteGlu5. There was a general decrease in these folate forms in the FPGS Os03g02030 knockout rice line while a dramatic increase was observed in overexpressed FPGS, cFBP and GNMT compared to Nipponbare in terms of 5-CH3-H4PteGlu4, 5/10-CHO-H4Pteglu5, 5-CH3-H4PteGlu6, and 5/10-CHO-H4Pteglu6 levels, resulting in a 2.5 to 8.8-fold increase in the total folate pool in the unpolished grains of rice. This study looked at the role of the two FPGS genes (Os03g02030 and Os10g35940) found in rice and the possible effect of introducing folate binding proteins (cFBP and GNMT) in terms of the overall folate profile in rice which can be exploited in breeding programmes designed to enhance folate content in staple crops like rice.

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May, Leigh A. "The production and characterisation of transgenic disease models for retinal ocular neovascularisation." University of Western Australia. Centre for Ophthalmology and Visual Science, 2004. http://theses.library.uwa.edu.au/adt-WU2006.0047.

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[Truncated abstract] One of the barriers to understanding and preventing proliferative diabetic retinopathy in humans has been the lack of an appropriate animal model. Historically dog, rat and mouse models of diabetic retinopathy have been studied but none of these exhibit the later changes of proliferative diabetic retinopathy. Animals can be rendered diabetic by surgical pancreatectomy or the use of chemicals such as allozan or streptozotocin or by feeding of a high galactose diet. Alternatively, spontaneous rodent models of diabetes have been examined such as the BB rat, KK mouse or NOD mouse. However, in each case the retinal vascular changes observed are those of early nonproliferative diabetic retinopathy comprising at most saccular microaneurysms, increased thickness of the capillary basement membrane, acellular capillaries and pericyte ghosts. … Fluorecein angiography of this transgenic line clearly demonstrates the presence of leaky new vessels, by the appearance of leakage spots scattered throughout the retina from 1 month of age. These mice constitute a valuable model of diabetic retinopathy. Neovascularization in this animal model is induced by VEGF as in human diabetic retinopathy. The source of VEGF in human diabetic retinopathy is the ischemic inner retina. In this transgenic model the source of VEGF are the photoreceptor cells, which are situated just underneath the inner retina. The neovascularization is not dependent on a particular developmental stage and there is no spontaneous regression of new vessels. Thus any results generated in this model are highly relevant to human diabetic retinopathy.

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Wilbert, Friederike Kristin [Verfasser]. "Development of a transgenic animal model for measurement of intra-cellular ATP / Friederike Kristin Wilbert." Berlin : Medizinische Fakultät Charité - Universitätsmedizin Berlin, 2017. http://d-nb.info/1148426116/34.

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Ravache, Thaís Terpins, Renata Simões, and Marcelo Demarchi Goissis. "Geração de animais transgênicos por inoculação de vetor viral em meio de cultura de óvulos." reponame:Repositório Institucional da UFABC, 2014.

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Orientador: Prof. Dr. Marcelo Augusto Christoffolete
Dissertação (mestrado) - Universidade Federal do ABC, Programa de Pós-Graduação em Biotecnociência, 2014.
Desde o século XV, animais fazem parte da rotina na área da pesquisa, principalmente para estudos de doenças, e hoje em dia o modelo animal mais utilizado para estes estudos é o camundongo, tendo uma participação em mais de 90% das pesquisas em todo o mundo, sendo considerado como uma primeira via para definir funções de genes em mamíferos. Os camundongos são considerados os principais modelos nas técnicas de transgenia animal, porém estas técnicas ainda estão em desenvolvimento, uma vez que as metodologias hoje utilizadas para a geração de animais transgênicos ainda se encontram com uma taxa de sucesso considerada baixa e são dispendiosas, necessitando de muitas etapas. Uma das dificuldades é o contato com a membrana do óvulo devido a zona pelúcida, que é considerada uma barreira física. Vetores virais estão em evidência nas técnicas de transgenia animal, sendo o lentivírus o mais utilizado. Portanto, o objetivo deste projeto é estabelecer um protocolo para a integração de DNA exógeno em óvulos por infecção lentiviral, anteriormente a fertilização in vitro juntamente com a técnica de dissecção parcial da zona pelúcida. Como vetor foi utilizado um lentivírus com GFP em sua construção. Para ocorrer a fertilização in vitro, foram feitas coletas de óvulos em camundongos fêmeas da linhagem C57BL/6, tratadas com injeções hormonais, e coletas de espermatozoides em machos desta mesma linhagem. Os óvulos obtidos foram divididos em grupos controle e com dissecção parcial da zona pelúcida, e estes foram subdivididos em grupos com e sem infecção lentiviral. Entre os grupos houve variação de 20% a 56,25% de embriões em estágio de duas células, e em alguns grupos foi possível alcançar o estágio de blastocisto eclodido. Porém não foi possível visualizar a emissão de fluorescência para confirmar a infecção lentiviral. Em conclusão as metodologias utilizadas tanto para a fertilização in vitro como para a dissecção parcial da zona pelúcida foram de sucesso. Porém a integração do DNA exógeno mostrou resultados não conclusivos, necessitando de estudos futuros.
Since the XV century, animals are used routinely in research, mainly for diseases studies, and nowadays the most used animal model is the mouse, which one has more than 90% of participation in researches around the world and it is considered the first track to define gene function in mammals. Mouse is the main model in transgenic techniques, however the methods available to generate transgenic animals still have a considerable low rate, and also it is expensive, requiring many degrees. An ordinary issue is the contact with the membrane of oocyte due zona pellucida that is considered a physical barrier. In transgenic animals technique, it is in evidence the utilization of viral vectors, and the most used are the lentiviruses. Therefore, the objective of this project is to establish a protocol for the integration of exogenous DNA by lentiviral infection into oocytes, before the in vitro fertilization, using the technique of partial dissection of the zona pellucida. It was used as a vector a lentivirus with GFP in your construction. For in vitro fertilization, were collected oocytes from C57Bl/6 mice, treated with hormones, and sperm from males of the same strain. The obtained oocytes were divided in control group and partial dissection of the zona pellucida group, and then subdivided in groups with and without lentiviral infection. Between the groups, was achieved 20% to 56,25% of two cells stage embryo, and hatched blastocysts stage were obtained at some groups. Therefore it was not possible to visualize florescence emission to confirm the lentiviral infection. In conclusion we have a practicable protocol for in vitro fertilization and partial dissection of the zona pellucida, reaching blastocysts stages in two groups. However the integration of exogenous DNA results were inconclusive, requiring further studies.

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Regensburger, Martin [Verfasser], and Beate [Akademischer Betreuer] Winner. "Adult neurogenesis in transgenic animal models of DYT1 primary torsion dystonia / Martin Regensburger. Betreuer: Beate Winner." Regensburg : Universitätsbibliothek Regensburg, 2011. http://d-nb.info/1022872877/34.

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Tsang, Kwok-yeung, and 曾國揚. "Molecular pathogenesis of abnormal chondrocyte differentiation in a transgenic mouse model." Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2006. http://hub.hku.hk/bib/B4501551X.

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Tang, Zhi. "Mass spectrometry-based metabolomics to unravel alterations in hepatic cell lines and transgenic mouse model of Alzheimer's disease." HKBU Institutional Repository, 2016. http://repository.hkbu.edu.hk/etd_oa/269.

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Chapter 5 reported the study to assess whether the urinary metabolic alterations linked to early pathophysiological changes in the TgCRND8 mouse model of AD. An unbiased metabolomics approach using high resolution Orbitrap mass spectrometry coupled with hydrophilic interaction liquid chromatography was conducted to uncover the metabolic alterations as a relevant readout of biochemical activity that implicated in the pathogenesis and progression of AD in the TgCRND8 mice. A total of 73 differential metabolites of urine sample sets was identified in 12-week and 18-week transgenic mice compared to wild-type littermates, covering perturbations of aromatic amino acids metabolism, TCA cycle and one-carbon metabolism. Of particular interest, divergent tryptophan metabolism, such as up-regulation of serotonin pathway while down-regulation of kynurenine pathway, was observed. The accumulation of both N-acetylvanilalanine and 3-methoxytyrosine indicated the aromatic L-amino acid decarboxylase deficiency. The microbial metabolites derived from tryptophan metabolism and drug-like phase II metabolic response via the glycine conjugation reactions were also highlighted, indicating that genetic modification in mouse brain not only alters genotype but also disturbs gut microbiome. Together, our study demonstrated that the integrative approach employing mass spectrometry-based metabolomics and a transgenic mouse model for AD might provide new insights into the metabolic phenotypes of AD with a noninvasive approach.;For cancer metabolism research, much effort has been focused on development of ultrahigh performance liquid chromatography triple quadrupole mass spectrometry (UPLC-MS/MS)-based targeted metabolomics method and its emerging applications in exploiting oncogene-induced metabolic alterations. To achieve our goal, more than one hundred intermediate and/or metabolite were selected and broadly categorized into cationic species and anionic species. Tandem mass spectrometric conditions were extensively optimized for each analyte by using energy-resolved collision-induced dissociation. Two crucial operating parameters of tandem mass spectrometry, namely, cone voltage and collision energy were finely tuned to get the highest signal response of the parent ion and fragment ions. Multiple reaction monitoring (MRM) transitions were created for each targeted compound, providing foundation for MRM-based assays. Meanwhile, to enhance the retention and separation of the water-soluble metabolites on reversed-phase C18 column, hydrophobic ion-pairing interactions separation (HIPS) strategies were proposed and established via complementary use of two ion-pairing reagents, heptafluorobutyric acid and tributylamine, for the cationic species and anionic species, respectively. The HIPS strategies led to efficient retention and resolution of polar intermediates/metabolites, covering the majority of components involved in central carbon metabolism and amino acid metabolism. Even isomeric pairs, like citrate-isocitrate and leucine-isoleucine, were almost baseline resolved. The performance evaluation of the developed UPLC MRM-based assays showed that nanomolar levels of limit of quantification were achieved. The developed methods enabled quantitative analysis of central carbon metabolism in mammalian cells. The altered metabolism induced by the overexpression of the oncogene EIF5A2 in human normal liver cell line LO2 was studied. We found that the altered aerobic glycolysis and pentose phosphate pathway dysregulated the tricarboxylic acid (TCA) cycle and amino acid imbalances presented as distinct metabolic features in EIF5A2 overexpressed LO2 cells.;In chapter 3, we performed quantitative analysis of central carbon metabolism and amino acid metabolism via the established UPLC-MRM-based metabolomics, which was combined with pharmacological inhibition of the catalytic enzymes, O-linked N-acetylglucosamine transferase (O-GlcNAc transferase, OGT) and β-N-acetylglucosaminidase (O-GlcNAcase, OGA) in order to uncover the contribution of protein (including the glycolytic enzymes) O-GlcNAc modification to metabolic alterations in cancer cells. We found that OGA inhibition led to decreased levels of intermediates in both glycolysis and TCA cycle, but increased level of pentose phosphate pathway. Interestingly, the opposite phenotypes were obtained in OGT inhibition, i.e., the increased levels of glycolysis and TCA cycle were observed. Our data suggested that O-GlcNAc modification could direct switches of glucose metabolism through coordinated glycolysis and TCA cycle pathways in HCC cell line.;In Chapter 4, an improved UPLC-MS/MS method for accurate and rapid assessment of the content and redox state of coenzyme Q10 (CoQ10) and the crucial component of electron transport chain (ETC) was described. Non-aqueous reversed phase liquid chromatography on a C18 column was hyphenated with tandem mass spectrometry working in the electrospray ionization positive MRM mode, with methanol serving dual roles as sample preparation solvent and mobile phase. This rapid extractive and analytical method could avoid artificial auto-oxidation of reduced form of CoQ10, enabling the native redox state assessment. To demonstrate the utility of the developed method, 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) exposed mice liver tissue were analyzed, revealing the down-regulated mitochondrial ETC in TCDD exposed mice group.;This thesis research concentrates on the development and applications of mass spectrometry-based metabolomics to elucidate biochemical alterations involved in basic research models for two common human diseases: mammalian cell culture model of hepatocellular carcinoma (HCC) and transgenic mouse model of Alzheimer's disease (AD). Two major approaches were developed: (1) targeted quantitative metabolomics for elucidation of altered cancer metabolism in human liver cell lines caused by the overexpression of the oncogene eukaryotic translation initiation factor 5A2 (EIF5A2) and O-Linked β-N-acetylglucosamine (O-GlcNAc) modification; (2) non-targeted metabolite profiling for early discovery of potential non-invasive urinary metabolite markers in the transgenic mouse model TgCRND8 of AD.

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García-Lareu, Belén. "Physiopathological and molecular characterization of a transgenic mouse overexpressing TNFalpha in schwann cells reveals a model for chronic peripheral neuropathy." Doctoral thesis, Universitat Autònoma de Barcelona, 2017. http://hdl.handle.net/10803/461995.

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Se ha relacionado la implicación de Tumor Necrosis Factor (TNF) alpha en la patogénesis de la neuropatía diabética periférica (DPN) así como en otras enfermedades inflamatorias cursadas con desmielinización y dolor neuropático. TNF-∝ es una citoquina proinflamatoria que puede actuar a diferentes niveles en el proceso de desmielinización. Tras una lesión en el nervio periférico, las células de Schwann producen esta citoquina en el sistema nervioso periférico (PNS) y se secreta localmente para atraer y activar a los macrófagos circulantes hacia la lesión, contribuyendo así a la degeneración Walleriana. En diferentes neuropatías periféricas conocidas, el incremento de los niveles de TNF-∝ en plasma se encuentran implicados en la progresión maligna de la enfermedad. Estudios en ratas inyectas con TNF-∝ directamente en el nervio ciático, demuestran una inflamación local seguida de desmielinización y degeneración axonal. Además, la administración de TNF-∝ ocasiona hiperalgesia mecánica aguda, una de las principales características del dolor neuropático, así como se ha postulado a TNF-∝ como biomarcador de dolor tras lesión nerviosa. Hoy en día no existen terapias efectivas para frenar y revertir la degeneración axonal y el dolor que cursan las neuropatías. Datos preclínicos obtenidos con los modelos animales actuales demuestran la carencia de un modelo óptimo y de los parámetros adecuados para establecer la patogénesis de la enfermedad. La obtención de un modelo animal apropiado es crítico para mimetizar las neuropatías periféricas humanas. Aunque el incremento mundial de la prevalencia de la diabetes ha potenciado el desarrollo de numerosos modelos, las principales discrepancias para la obtención de un correcto modelo in vivo para las neuropatías asociadas a la Diabetes Mellitus, residen en las importantes diferencias anatómicas y la esperanza de vida entre humanos y roedores. Con el objetivo de caracterizar los efectos de TNF-∝ en el desarrollo de neuropatía periférica crónica y dolor neuropático, se generó un ratón transgénico que sobreexpresa TNF-∝ en células de Schwann, bajo control del promotor de la proteína de la mielina P0. En el trabajo que se presenta a continuación se caracteriza la sobreexpresión de TNF-∝ en las células de Schwann pro-mielinizantes en diferentes estadíos de mielinización (a 5, 21 y 65 días de vida), reflejando que los altos niveles alcanzados en los nervios ciáticos transgénicos ocasionan una desregulación de las principales proteínas de la mielina (P0, MBP, PMP22, MAG), correlacionando con una desestructuración de la vaina de mielina y el incremento de células positivas para p75NTR, marcador específico de células de Schwann inmaduras y no-mielinizantes. También detectamos una inflamación local debido a una una alta infiltración de macrófagos en nervios ciáticos y médula espinal en estos animales. Tras la lesión del nervio ciático, la recuperación de la función motora y posterior remielinización se retrasa en los ratones transgénicos, como demuestra la evaluación mediante el Sciatic Functional Index, y los test electrofisológicos. Sin embargo, estudios de algesimetría muestran inalterada la nocicepción frente a estímulos mecánicos, aunque los ratones transgénicos presentan hipersensibilidad ante estímulos térmicos, incrementada tras la lesión y correlacionada con la activación microglial y astrocitaria en la médula espinal. Además, se detectaron altos niveles de BDNF and CCL2, junto con una sobreexpresión de los canales iónicos Nav1.7 y Nav1.8, relacionados con dolor. Estudios morfométricos no reflejan diferencias en el tamaño de los nervios, ni siquiera tras la lesión, aunque los animales transgénicos sí presentan una ligera reducción en el diámetro axonal y un menor grosor de la mielina. Por consiguiente, este modelo podría ayudar a elucidar el papel de TNF-∝ en el desarrollo de dolor, la regeneración y las neuropatías periféricas, así como en el desarrollo de nuevas terapias eficientes para paliar estas patologías.
Tumor Necrosis Factor (TNF) alpha has been implicated in the pathogenesis of diabetic peripheral neuropathy (DPN), among other inflammatory demyelinating diseases and neuropathic pain. TNF-∝ is a pro-inflammatory cytokine that can act at several steps in the demyelination process. It is produced by Schwann cells in the peripheral nervous system (PNS) after nerve injury and released into the local environment to attract and activate macrophages at the site of injury, contributing to Wallerian degeneration and demyelination. An important observation in different peripheral neuropathies is the increased levels of TNF-∝ in plasma, being implicated in the onset and/or malignant progression of peripheral nerve diseases. In vivo studies demonstrated a local inflammation in the sciatic nerve of rats after injection of TNF-∝, followed by demyelination and axonal degeneration. Furthermore, the administration of TNF-∝ resulted in acute mechanical hyperalgesia, a main characteristic of neuropathic pain and therefore TNF-∝ is postulated as a biomarker for painful alterations after nerve injury. Nowadays, there is not an effective therapy to stop and reverse the axonal degeneration and pain that characterize peripheral neuropathies. Unfortunately, the preclinical data using animal models demonstrated the lack of optimum models and outcome measures to underlay the pathogenesis of the disease. An appropriate animal model is critical for replicating the essential features of peripheral neuropathies, understanding DPN pathophysiology and to develop effective strategies. Although the increasing worldwide prevalence of diabetes has fueled the development of several mouse models, the main discrepancies related to the proper generation of a mouse model for the study of peripheral neuropathies, and complications of DM, like diabetic peripheral neuropathy, are a consequence of the anatomical differences and the incomparable life expectancies between humans and rodents. With the aim to characterize TNF-∝ effects in the development of peripheral neuropathy and chronic neuropathic pain, a transgenic mouse model overexpressing TNF-∝ in Schwann cells, under the peripheral myelin protein P0 promoter, was generated. Here we characterized the overexpression of TNF-∝ in myelinated Schwann cells at different stpes of myelination (postnatal days 5, 21 and 65) showing that high levels of TNF-∝ in sciatic nerve leads to the downregulation of the major PNS myelin proteins (P0, MBP, PMP22, MAG) compared to wild type mice, correlating with the loss of structured myelin and an increase in p75NTR in the sciatic nerve, a marker for immature and non-myelinated Schwann cells. Local inflammation was also demonstrated by high levels of macrophage infiltration in both sciatic nerve and spinal cord, compared with wild type animals. Furthermore, stress conditions were induced by sciatic nerve crush after which recovery and subsequent remyelination were delayed in the transgenic mice, as evaluated by the Sciatic Functional Index and electrophysological tests. On the other hand, algesimetrical tests revealed unaltered mechanical nociception, with or without injury, although transgenic animals showed thermal hypersensivity, higher after peripheral injury, correlating with the microglial and astrocyte activation in the spinal cord. Moreover, high expression of BDNF and CCL2, as well as overexpression of Nav1.7 and Nav1.8 channels, all related to the maintenance of chronic inflammatory pain, were detected in DRGs of TNF-∝ transgenic mice. A morphometrical study of tibialis nerves showed no differences in the total nerve surface between genotypes and injury. However, transgenic mice exhibited a slight reduction in the axonal diameter and a significant thinner myelin sheath than wild type animals. This model could be helpful in the characterization of the role TNF-∝ in pain development, injury and DPN as well as in developing efficient therapeutic strategies to modulate such pathological conditions.

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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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Shamy, David Stephen. "Local Knowledge and the Social Dimensions of Risk. The Case of Animal Biopharming in New Zealand." Thesis, University of Canterbury. Political Science and Communication, 2006. http://hdl.handle.net/10092/893.

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This thesis analyses the social dimensions of the risk of animal biopharming (the genetic modification of animals to produce pharmaceuticals) in New Zealand, in the context of a wider discussion of the social nature of risk. In doing so, it offers a different conception of risk and risk assessment than is currently used within the government policy of New Zealand. Current policy has focused on technical evaluations of risk, in which the technology being analysed is not assessed within the social context it will enter and risk is compartmentalised into quantifiable and standardised data. This approach both serves to legitimate "experts" as the true judge of risk, and also isolates members of the wider public to the realm of "ethical" discussion and participation. Such policy, I argue, does not lend itself to good decision-making, as risk management procedures, built on the back of risk assessment, often prove to be impractical when entering complex and ambiguous social environments. Likewise, this form of risk assessment often fails to account for risk that could be identified by those with in-depth knowledge of the environment, both social and physical, that the technology will enter. This thesis pilots aspects of an alternative approach, which aims to elicit information about the relevant environment. It demonstrates how one might identify and interview those with what is termed here as "local knowledge", and how that knowledge can make a significant contribution to risk identification and assessment and the identification of social implications. The thesis concludes not only that local knowledge can contribute practically to risk assessment, but also that the concepts of risk and expertise must be widened to include social and contextual behaviour and knowledge.

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Sawafta, Ashraf. "Design of vector for the expression of shRNA in transgenic animals." Phd thesis, Université Pierre et Marie Curie - Paris VI, 2008. http://tel.archives-ouvertes.fr/tel-00812776.

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Les petits ARN interférents (siRNA) sont encore rarement utilisés chez les vertébrés transgéniques pour inhiber l'expression de gènes. En effet, les vecteurs contenant un promoteur de type ARN polymérase III comme ceux des gènes U6 et H1 qui permettent une expression élevée des gènes codant pour des ARNi dans des cellules sont souvent silencieux in vivo. Dans cette thèse, divers vecteurs exprimant des petits ARN double brins (shRNA) ont été testés dans des cellules en culture et chez des souris transgéniques pour inhiber l'ARN m du gène précoce IE du virus de la pseudo rage porcine responsable de la maladie d'Aujeszky. La quantité et la séquence des si RNA produits ont été étudiées par qPCR. Dans des cellules CHO transfectées pour une expression transitoire, les vecteurs contenant les gènes U6-shRNA ont été de loin les plus efficaces pour inhiber le gène IE en raison du niveau élevé de siRNA produit. Par ailleurs, deux constructions contenant le promoteur de type ARN polymérase II, le promoteur du gène eF1-α etune séquence de shRNA bordée par 5T ou introduite dans un gène de microARN (miRNA) le miR30 ont permis d'obtenir une inhibition significative mais limitée de l'ARNm du gène IE. Ceci parait être du au niveau relativement faible de siRNA produit. Le siRNA produit par le gène du miRNA s'est avéré aussi efficace que ceux obtenus à partir des constructions U6-shRNA bien que ces derniers soient un peu plus longs. Ces diverses constructions ont été utilisées pour obtenir des souris transgéniques. Des souris contenant la séquence du shRNA n'ont pu être obtenues qu'à partir de la construction miRNA. Ceci peut être du au fait que les siRNA produits par les autres constructions ont exercé un effet inhibiteur sur des cibles aspécifiques (off-targeting) qui ne s'est pas produit avec le siRNA provenant de la construction miRNA car il contient quelques nucléotides en moins. Les souris transgéniques contenant la construction miRNA ont été soumises à une infection par le virus de la pseudo rage porcine. Bien que les souris exprimaient le gène shRNA qu'à un faible niveau. Quelques souris transgéniques ont résisté à l'infection. La seconde partie de la thèse a consisté à sélectionner d'autres séquences de shRNA capables d'inhiber l'expression du gène IE sans exercer des effets aspécifiques. Deux séquences de shRNA ont permis une telle inhibition. L'une est dirigée contre la région 5'UTR du gène IE et l'autre contre la région 3'UTR. Ces données suggèrent que (1) l'efficacité d'un shRNA n'est pas déterminée par sa séquence d'une manière totalement prévisible (2) l'efficacité d'un siRNA est d'autant plus élevé que sa séquence cible dans l'ARNm est en structure double brin (3) un effet inhibiteur intense et optimum peut être obtenu avec des concentrations faibles d'un siRNA (4) les effets secondaires et en particulier le off-targeting peuvent avoir lieu à faible concentration du siRNA mais ils ont d'autant plus de chance de se produire que la concentration du si RNA est plus élevée (5) un siRNA destiné à être utilisé chez des animaux transgéniques devrait être choisi pour sa capacité à inhiber efficacement un gène à faible concentration pour réduire ses effets secondaires.

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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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Alli, Zaman. "The assembly of hepatitis B virus core particles in transgenic tobacco, carrot and rice plants." Thesis, University of Ottawa (Canada), 2004. http://hdl.handle.net/10393/29072.

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The spread amongst humans of viral diseases such as acquired immunodeficiency syndrome (AIDS), hepatitis and severe acute respiratory syndrome (SARS) is alarming. A plant-based high fidelity production system is being developed with emphasis on producing antigens capable of being orally delivered to humans in plant packets. To test whether transgenic tobacco, carrot and rice plants can correctly process and assemble the hepatitis-B virus (HBV) core particle/antigen (HBcAg), they were transformed with a C-terminal truncated version of the HBcAg subunit coding sequence. Transgenic tobacco, carrot and rice plants processed the HBV subunits accurately indicating that these recombinant expression systems can be extended to produce other proteins at reduced costs. In the wild-type expression construct (H1); the enhanced cauliflower mosaic virus double 35S (CaMV-d35S) promoter was fused to the alfalfa mosaic virus RNA 4 (AMV-RNA4) sequence to achieve greater translation of a C-terminal truncated HBV core particle subunit. A second expression construct (H2) was plant-codon optimized to match the Arabidopsis thaliana plant genome codon preferences. A third codon-optimized expression construct (H3) had a KDEL (lysyl-aspartyl-glutamyl-leucine) encoded sequence. While a fourth expression construct (H4) included an extensin signal sequence in place of the AMV-RNA4 sequence. Western blotting analysis showed the presence of the HBcAg in transgenic tobacco, carrot and rice plants. The HBcAg levels increased from the H1 to the H4 transgenic tobacco lines. Plant codon-optimization of the HBcAg sequence and addition of the KDEL encoded sequence led to higher levels of HBcAg. The most effective modification was observed when the extensin signal sequence replaced the AMV-RNA4 translation enhancer sequence resulting in the highest observed yields of HBcAg in both the leaves and seeds of the best H4 tobacco plant. In edible plants, higher levels of HBcAg were observed in carrot roots as opposed to carrot leaves and in rice seeds as opposed to rice leaves. Further analyses via electron microscopy indicated that the HBV subunits had assembled into virus-like particles of 25--30 nm diameter in all three plant systems. Therefore, these studies may aid in the global quest to develop cheap, safe and effective vaccines.

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17

Chen, Paula Renee. "Muscle Fiber Hyperplasia in Leg Muscle of Transgenic Quail Overexpressing anAlternative Splicing Variant of Myostatin." The Ohio State University, 2016. http://rave.ohiolink.edu/etdc/view?acc_num=osu1462207424.

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Suen, Fung Ki. "Tyrosine hydroxylase-green fluorescence protein transgenic zebrafish as a biosensor and animal model for nicotine and ketamine drug effects." HKBU Institutional Repository, 2012. https://repository.hkbu.edu.hk/etd_ra/1449.

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19

Chen, Yuk-shan, and 陳玉珊. "Role of aldose reductase in pathogenesis of diabetic neuropathy by making use of Thy1-YFP transgenic mice with aldose reductase-mutation." Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2005. http://hub.hku.hk/bib/B36371191.

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20

Milliken, Erin Lee. "Use of a transgenic mouse mode of ovarian hyperstiumluation [sic] to identify therapeutic targets and mechanisms in hormone-induced mammary cancer /." Connect to text online, 2005. http://rave.ohiolink.edu/etdc/view?acc%5Fnum=case1121273034.

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21

Shirwany, Najeeb A. "Neurotoxicity induced by A[beta] 40 and A[beta] 42 in transgenic mouse models of Alzheimer's disease." Oklahoma City : [s.n.], 2009.

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22

Mousavi, Malahat. "Characterization and expression of subtypes of nicotinic receptors in brain and adrenal medulla : with focus on development, Alzheimer's disease and transgenic animal models /." Stockholm, 2003. http://diss.kib.ki.se/2003/91-7349-616-2/.

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23

Sjuve, Rolf. "Function of contractile and cytoskeletal proteins in smooth muscle effects of hypertrophy and age and of desmin removal in a transgenic animal /." Lund : Dept. of Physiology and Neuroscience, Lund University, 1998. http://books.google.com/books?id=ccFqAAAAMAAJ.

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24

Woodfint, Rachel M. woodfint. "Identification of the LB-FABP promoter as a liver specific promoter via the generation of transgenic quail expressing eGFP within their liver cells." The Ohio State University, 2018. http://rave.ohiolink.edu/etdc/view?acc_num=osu1523880800285644.

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25

Kezic, Jelena Marie. "A study of the monocyte-derived cell populations of the uveal tract and retina in homeostatic conditions and during the early stages of ocular autoimmune disease." University of Western Australia. School of Anatomy and Human Biology, 2008. http://theses.library.uwa.edu.au/adt-WU2009.0084.

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The eye contains closely related but widely different tissues, offering a unique opportunity to investigate the phenotype and function of monocyte-derived cell populations within functionally unique microenvironments in a single complex organ. The uveal tract and retina contain rich networks of immune cells that reside and traffic through the eye, these cells having been implicated in various ocular inflammatory processes and immune-mediated diseases. One such inflammatory condition is human posterior uveitis, an autoimmune disease mainly affecting the retina. As current treatments for posterior uveitis only serve to slow down disease progression, studies using animal models, namely, experimental autoimmune uveoretinitis (EAU), have focused on determining the key cellular and molecular mediators involved in disease initiation in order to expand the potential for novel therapeutic applications. The overall purpose of experiments in this thesis was to explore monocyte-derived cell populations of the uveal tract and retina, this being achieved by utilising a novel transgenic mouse model. Cx3cr1gfp/gfp transgenic mice on both BALB/c and C57Bl/6 backgrounds contain an enhanced green fluorescent protein (eGFP) encoding cassette knocked into the Cx3cr1 gene, disrupting its expression but facilitating GFP expression under the control of the Cx3cr1 promoter. Heterozygous (Cx3cr1+/gfp) mice were generated by crossing Cx3cr1gfp/gfp mice to wild-type (WT) mice. This transgenic model allowed for the exquisite visualisation of Cx3cr1-bearing monocyte-derived dendritic cells (DC) and macrophages in ocular tissues, whilst also enabling the investigation of a potential role for Cx3cr1 in recruiting monocyte-derived cells to the eye in steady-state and inflammatory conditions.

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26

Ng, Hang-pong, and 伍恆邦. "Development of murine model of autoimmune thyroiditis induced with homologous thyroid peroxidase and evaluation of immune tolerance in atransgenic mice that overexpress mTPO in the thymus." Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2005. http://hub.hku.hk/bib/B35772554.

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27

Lu, Song, and 鲁嵩. "Phenotype analysis of Pdss2 conditional knockout mouse." Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2010. http://hub.hku.hk/bib/B45552381.

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28

Herbach, Nadja. "Clinical and pathological characterization of a novel transgenic animal model of diabetes mellitus expressing a dominant negative glucose-dependent insulinotropic polypeptide receptor (GIPR dn)." Diss., lmu, 2002. http://nbn-resolving.de/urn:nbn:de:bvb:19-10080.

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29

Costa, David Antonio. "Promoting and preventing alzheimer's disease in a transgenic mouse model : apolipoprotein e and environmental enrichment /." [Tampa, Fla.] : University of South Florida, 2005. http://purl.fcla.edu/fcla/etd/SFE0001179.

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30

Fehlings, Christiane [Verfasser]. "Physiological and morphological characterization of transgenic pigs expressing a dominant-negative glucose-dependent insulinotropic polypeptide receptor (GIPRdn) - a large animal model for diabetes research / Christiane Fehlings." München : Verlag Dr. Hut, 2010. http://d-nb.info/1009095366/34.

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31

Braun-Reichhart, Christina Franziska Maria Verfasser], and Eckhard [Akademischer Betreuer] [Wolf. "Genotypic and phenotypic characterization of INSC94Y transgenic pigs : a novel large animal model for permanent neonatal diabetes mellitus / Christina Franziska Maria Braun-Reichhart. Betreuer: Eckhard Wolf." München : Universitätsbibliothek der Ludwig-Maximilians-Universität, 2013. http://d-nb.info/1045152943/34.

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32

Schramke, Sarah [Verfasser]. "The Libechov Minipig as a transgenic animal model for preclinical research in Huntington’s Disease : development of a phenotyping battery including cognitive, motor and behavioral assessments / Sarah Schramke." Hannover : Bibliothek der Tierärztlichen Hochschule Hannover, 2016. http://d-nb.info/1107037573/34.

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33

Ruivo, Pedro Reis. "Aging pathology in sprague dawley rats : background lesions and comparative study between wild type and transgenic rats with neuronal overexpression of human adenosine A2A receptors." Master's thesis, Universidade de Lisboa, Faculdade de Medicina Veterinária, 2018. http://hdl.handle.net/10400.5/16691.

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Dissertação de Mestrado Integrado em Medicina Veterinária
Aging is a complex phenomenon defined as a time-dependent functional decline, progressive loss of physiological integrity and progressive increase in disease susceptibly. Adenosine A2A receptors (A2AR) are G protein-couple receptors that, upon binding of adenosine, lead to different transducing signals. Although having a protective effect, A2AR also play an important role in neurodegenerative disorders and are upregulated in the brain of Alzheimer and Parkinson patients. Previous studies from our collaborators showed that transgenic rats with neuronal overexpression of human A2AR (Tg (CaMKIIhA2AR)) have depressive-like behavior, impaired hypothalamic-pituitary-adrenal (HPA) axis and, as a result of this, increased levels of circulating corticosteroids. The aim of this work was to evaluate, by histopathology, the impact of the neuronal overexpression of human A2AR in the onset of specific or age-associated lesions in transgenic Sprague Dawley rats. Comprehensive necropsy and histopathology were performed in 37 Wild-type (Wt) and 39 transgenic (Tg) rats, at specific time-points, ranging from 12 to 126 weeks of age. Univariate and multivariate statistical analysis were performed to investigate the association between the phenotype and genotype. Briefly we found that Tg rats are 2.7 times more likely to develop systemic pathology than Wt rats [Odds ratio (OR) 2.745, IC 95% 1.0.07-6.997; (p<0.05)]. In the heart cardiomyopathy was the most frequent lesion both in Wt and Tg rats, and its incidence did not differ between groups [OR 0.82; IC 95% 0.315-2.139, (p>0.05)]. In blood vessels, mineralization was the most frequent lesion and Tg rats were 5.5 times more likely to develop this lesion than Wt [OR 5.486, IC 95% 1.776- 17.074; (p<0.05)]. In lung, alveolar histiocytosis and alveolar septa mineralization were the most frequent lesions and Tg rats were 7.7 times more likely to develop lung pathology than Wt [OR 7.7, IC 95% 1.604-37.19; (p<0.05)]. In kidney, chronic progressive nephropathy was the most frequent lesion both in Wt and Tg rats, and its incidence did not differ between groups [OR 2.5, IC 95% 0.919-6.923; (p>0.05)]. Regarding adrenal gland pathology, vacuolation of the cortical cells was the most frequent lesion and Tg rats were 4.3 times more likely to develop this pathology than Wt [OR 4.3, IC 95% 1.156-16.248; (p<0.05)]. Mammary fibroadenoma was the most common tumor in our sample, being observed in one Wt and five Tg rats. Even in cases where no difference was seen when comparing Tg and Wt rats, all lesions found in our study were age-associated lesions, typical for this species, and their incidence correlated with age. Our results show a clear correlation between increased A2AR signaling in the brain and accelerated aging, in our sample, and although herein we did not explore the precise mechanism(s) through which this occurs, it could be linked to the fact that Tg rats have HPA-axis dysfunction and increased circulating levels of corticosterone, which translated into chronic stress. To our knowledge, this is the first study to characterize the systemic repercussion of neuronal overexpression of adenosine A2A receptors, which is seen in several degenerative disorders during the aging process.
RESUMO - O envelhecimento é um fenómeno complexo definido como um declínio funcional dependente do tempo, com perda progressiva da integridade fisiológica e aumento gradual da suscetibilidade a doenças. Os recetores de adenosina A2A (A2AR) são recetores acoplados à proteína G cuja ligação à adenosina leva a diferentes sinais de transdução. Apesar do seu efeito protetor, os recetores de adenosina A2A têm também um papel crítico em doenças neurodegenerativas e estão sobre expressos no cérebro de doentes de Alzheimer e Parkinson. Estudos recentes demostraram que ratos transgénicos com sobre expressão neuronal de A2AR (Tg (CaMKIIhA2AR)) apresentam comportamento depressivo e disfunção do eixo hipotálamo-hipófise-adrenal, resultando em níveis elevados de corticosteroides circulante. O objetivo deste estudo foi avaliar, por histopatologia, o impacto da sobre expressão neuronal de A2AR no fenótipo de envelhecimento de vários órgãos e sistemas, em ratos Sprague Dawley. Foi efetuada a necrópsia compreensiva e histopatologia em 37 ratos “Wild type” (Wt) e 39 transgénicos (Tg) com idade variável entre as 12 e as 126 semanas. Foi efetuada análise estatística univariável e multivariável para investigar a associação entre o fenótipo e o genótipo. Resumidamente, descobrimos que os ratos Tg foram 2.7 vezes mais suscetíveis a desenvolver patologia sistémica, comparativamente aos Wt [Odds ratio (OR) 2.745, IC 95% 1.0.07-6.997; (p<0.05)]. No coração, a lesão mais frequentemente diagnosticada foi cardiomiopatia e a sua incidência não variou entre Wt e Tg [OR 0.82; IC 95% 0.315-2.139, (p>0.05)]. Nos vasos sanguíneos, a lesão mais frequente foi a mineralização da parede, sendo que os ratos Tg foram 5.5 vezes mais suscetíveis a desenvolver esta lesão que os Wt [OR 5.486, IC 95% 1.776- 17.074; (p<0.05)]. Relativamente ao pulmão, as lesões mais frequentes foram a histiocitose alveolar e a mineralização dos septos alveolares. Os ratos Tg foram 7.7 vezes mais suscetíveis a desenvolver estas lesões que os Wt [OR 7.7, IC 95% 1.604-37.19; (p<0.05)]. Relativamente ao rim, a lesão mais frequente foi a nefropatia crónica progressiva e a sua incidência não variou entre os ratos Wt e Tg [OR 2.5, IC 95% 0.919-6.923; (p>0.05)]. Relativamente às adrenais, a lesão mais frequente foi a vacuolização das células da cortical e os ratos Tg foram 4.3 vezes mais suscetíveis para o desenvolvimento desta lesão que os Wt [OR 4.3, IC 95% 1.156-16.248; (p<0.05)]. Fibroadenoma mamário foi o tumor mais frequente, tendo sido observado em um rato Wt e cinco ratos Tg. Mesmo em casos onde não foi observada diferença entre ratos Wt e Tg, todas as lesões encontradas neste estudo são lesões muitas vezes associadas ao envelhecimento, típicas desta espécie e a sua incidência correlacionou-se com a idade. Os nossos resultados mostram uma relação clara entre a sobre expressão neuronal de A2AR e envelhecimento acelerado na nossa amostra, e apesar de não termos explorado os mecanismos específicos para tal acontecimento, poderá estar ligado ao facto dos ratos Tg terem disfunção do eixo hipotálamo-hipófise-adrenal e níveis elevados de corticosterona, o que se traduz em stress crónico. A conhecimento dos autores, este é o primeiro estudo a caracterizar as repercussões sistémicas da sobre expressão neuronal de A2AR, que é observada em várias doenças degenerativas durante o envelhecimento.
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34

Schuldenzucker, Verena [Verfasser]. "The Libechov minipig as a transgenic animal model for preclinical research in Huntington’s disease – Results of an observational study comparing motor, cognitive, behavioral and metabolic endpoints / Verena Schuldenzucker." Hannover : Bibliothek der Tierärztlichen Hochschule Hannover, 2018. http://d-nb.info/1162650443/34.

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35

Marshall, Aiden Christopher James 1976. "The role of Fas and TNFα in experimental autoimmune gastritis." Monash University, Dept. of Pathology and Immunology, 2003. http://arrow.monash.edu.au/hdl/1959.1/9413.

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36

Ferlito, Valentina Claudia. "Evaluating the potential for neurodegenerative disease models in juvenile Drosophila melanogaster." Thesis, University of Edinburgh, 2017. http://hdl.handle.net/1842/28834.

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With 9.9 million new dementia cases each year, Alzheimer’s and Parkinson’s disease (AD and PD) are the most prevalent form of neurodegenerative disorder (NDG) affecting the aging population. Despite years of pharmaceutical research, no cure is yet available. Most neuropathological aspects of these diseases are extremely complex but the study of the rare genetic cases allowed to model these diseases in animals and uncover key pathophysiological processes. Transgenic Drosophila NDG models have been used for in vivo studies for many years with a range of relevant phenotypes. The cellular and molecular biology of the Central Nervous System, as well as the mechanisms underlying neurodegeneration, are well conserved between Drosophila and Humans (with a 75% of human disease-related genes having homologs in flies). Most NDG studies are performed in the aging flies. However, there are reports of measurable phenotypes for a variety of AD and PD models in juvenile Drosophila melanogaster (larval stage) with an unexploited considerable potential for drug discovery and screening for this outstanding model. Here I sought to develop a new assay for research into NDGs that focus on the earliest phenotypes. During this Ph.D. project a customized crawling assay apparatus was developed, for the assessment of locomotor ability in humanised larval Drosophila (overexpressing human proteins/peptides linked to AD and PD). A locomotor phenotype was identified in larvae overexpressing different variation of Amyloid-β42, tau and α-Synuclein pan neutrally: these animals crawl on agarose surface at a reduced mean speed when compared to controls. The defect was proven partially rescuable by administration of Tacrine and Methylene Blue, renewing the importance of such models for future applications in drug discovery and screening. The motor impairment supports the hypothesis of a neurotoxic effect of the protein/peptide. Thus, to test this further, the overexpression of the human transgenes was restricted to neurons involved in larval olfaction (olfactory impairment is often the earliest symptom in PD and AD) and odour associated learning tasks (both PD and AD are characterized by severe cognitive dysfunction). Interestingly, larvae overexpressing the Amyloid-β42 ARC peptide in the Olfactory Sensory Neurons showed a subtle navigation defect during chemotaxis (in 1-Hexanol odour gradient) that could possibly be addressed to premature neural habituation to the olfactory stimulus. Furthermore, the overexpression of the peptide in the larval Mushroom Bodies influenced the performances of the animals in associative learning tasks. Lastly, using immunohistochemistry and confocal imaging techniques I showed that the gross morphology of neurons is not altered by the targeted overexpression of the Amyloid-β42 ARC. Even though physiological studies are required to characterize the chemosensory/learning defect shown by the Amyloid-β42 ARC larvae, this Ph.D. work further confirms that the effects of the overexpression of the human transgenes are robust and measurable already at larval stage. These findings may also be relevant to the development of new, fast, and cost-effective compound screening procedures, for applications in early stages of the drug discovery process.

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37

Gupta, Meeta. "Consumer behavior towards chicken fed with genetically modified high available phosphorus (HAP) corn." Access to citation, abstract and download form provided by ProQuest Information and Learning Company; downloadable PDF file 1.87Mb, 129 p, 2005. http://wwwlib.umi.com/dissertations/fullcit/1428261.

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38

Ramain, Philippe. "Recherche des elements regulateurs du gene sgs3 de drosophila melanogaster par cartographie des sites hypersensibles a la dnasei et construction de lignees transgeniques." Université Louis Pasteur (Strasbourg) (1971-2008), 1989. http://www.theses.fr/1989STR13018.

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Le gene sgs3 de drosophila melanogaster est utilise comme modele pour l'etuden de l'expression differentielle d'un gene au cours du developpement. Ce gene, est regule par une hormone steroide, l'ecdysone, est fortement et exclusivement comprime dans les glandes salivaires de 3eme stade larvaire. L'etude de la regulation de sgs3 a ete abordee au niveau de la structure chromatinienne. Caracterisation des sites hypersensibles a la dnasei (dhs) dans la region du gene sgs3 en relation avec son activite dans les lignees sauvages de drosophile et mis aussi en evidence un complexe dhs respectivement a -750, -470 et -600 pb du site d'initiation de sgs 3 dont l'un "-600" est specifique de l'expression, alors que les deux autres sont profondement modifies lorsque le gene cesse d'etre exprime

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39

Russell, Christopher Glyn. "Improvement of expression of recombinant human protein C in the milk of transgenic animals using a novel transgene construct." Diss., Virginia Tech, 1993. http://hdl.handle.net/10919/37446.

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40

Myelnikov, Dmitriy. "Transforming mice : technique and communication in the making of transgenic animals, 1974-1988." Thesis, University of Cambridge, 2015. https://www.repository.cam.ac.uk/handle/1810/252737.

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41

Kissenpfennig, Adrien Nicolas. "PrP gene regulation in normal and transgenic animals." Thesis, University of Hertfordshire, 1998. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.267442.

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42

Harrison, Sharon Jane. "Targeted transgenesis and the 186 site-specific recombination system /." Title page, summary and contents only, 1999. http://web4.library.adelaide.edu.au/theses/09PH/09phh322.pdf.

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43

Roeske, Cassandra. "Role of the Heterotrimeric Go Protein Alpha-subunit on the Cardiac Secretory Phenotype." Thèse, Université d'Ottawa / University of Ottawa, 2013. http://hdl.handle.net/10393/24191.

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Atrial natriuretic factor (ANF) is a polypeptide hormone produced in heart atria, stored in atrial secretory granules and released into the circulation in response to various stimuli. Proper sorting of ANF at the level of the trans-Golgi network (TGN) is required for the storage of ANF in these specific granules, and this sorting of hormones has been found to be associated with G-proteins. Specifically, the Go protein alpha-subunit (Gαo) was established to participate in the stretch-secretion coupling of ANF, but may also be involved in the transporting of ANF from the TGN into atrial granules for storage and maturation. Based on knowledge of Gαo involvement in hormone production in other endocrine tissues, protein-protein interactions of Gαo and proANF and their immunochemical co-localization in granules, the direct involvement of these two proteins in atrial granule biogenesis is probable. In this study, mice were created using the Cre/lox recombination system with a conditional Gαo knockout in cardiocytes to study and characterize ANF production, secretion and granule formation. Deletion of this gene was successful following standard breeding protocols. Characterization and validation of cellular and molecular content of the knockout mice through mRNA levels, protein expression, peptide content, electron microscopy, and electrocardiography determined that a significant phenotypic difference was observed in the abundance of atrial granules. However, Gαo knockout mice did not significantly alter the production and secretion of ANF and only partially prevented granule biogenesis, likely due to incomplete Gαo knockout. These studies demonstrate an involvement of Gαo in specific atrial granule formation.

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44

Delpire, Veronique Charline. "Ethical schemes for the use of transgenic laboratory animals." Thesis, University of Nottingham, 2000. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.324118.

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45

Page, Raymond Lynn. "Evaluation of techniques for the production of transgenic animals." Diss., Virginia Tech, 1993. http://hdl.handle.net/10919/40112.

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46

Page, Raymond L. "Evaluation of techniques for the production of transgenic animals." Diss., Virginia Tech, 1993. http://hdl.handle.net/10919/40112.

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A polymerase chain reaction (PCR) technique was used to detect transgene presence after pronuclear microinjection of mouse zygotes cultured to various stages of development. The transgene was detected in 88% of 1-cell, 88% of 2-cell, 44% of 4-cell, 40% of morula, and 29% of blastocysts. By comparison, the integration frequency for transgenic mice made using the same DNA construct was 22%. After 5 days of in vitro culture, the injected construct was detected in 83% of arrested 1-cell, 85% of arrested 2-cell, and 85% of fragmented embryos. Only 28% of zygotes cultured after microinjection of DNA developed to the blastocyst stage compared to 74% of noninjected zygotes. When DNA buffer alone was injected, 63% of zygotes developed to the blastocyst stage. These data suggest that pronuclear microinjection of DNA is highly detrimental to subsequent embryonic development. Also, most injected DNA that is either unintegrated or that will not be integrated into the genome has been degraded by the blastocyst stage such that it can no longer be detected by PCR. The production of transgenic mice by cytoplasmic injection of DNA mixed with poly-L-lysine is also described. The effects of DNA concentration and stoichiometric ratio of positive charges provided by the polycation to negative charges provided by DNA on transgenic frequency and embryonic viability were studied. The highest transgenic frequency (13% of pups born were transgenic) was obtained when a polylysine/DNA complex having a stoichiometric charge ratio of one to one (equal positive charges as negative charges) at a DNA concentration of 50 ug/ml was used. The transgenic frequency by pronuclear injection of the same DNA construct was 22%. The percentage of zygotes, cultured in vitro, reaching the blastocyst stage which were injected cytoplasmicly was not different (p>0.05) than that of control zygotes that were not microinjected (65% versus 74%, respectively). The percentage of zygotes reaching the blastocyst stage after pronuclear microinjection with DNA at a concentration of 1.5 ug/ml was significantly lower (p<0.05) than control embryos (28% versus 74%, respectively). The overall transgenic pup production efficiency (percent of transgenic pups per embryos transferred) by cytoplasmic injection was 2.4% compared to 3.5% by pronuclear microinjection.
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47

Vize, Peter Darren. "Expression of porcine growth hormone in bacteria and transgenic animals." Title page, contents and summary only, 1987. http://web4.library.adelaide.edu.au/theses/09PH/09phv864.pdf.

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48

Blomberg, Patrik. "Non-target Effects of Genetically Modified Trees." Doctoral thesis, Umeå : Department of Ecology and Environmental Science, Umeå Universitet, 2007. http://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-1348.

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49

Vernet, Muriel. "Specificite transcriptionnelle et demarrage de l'activite du genome chez les mammiferes." Paris 6, 1992. http://www.theses.fr/1992PA066357.

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Chez la souris, le genome zygotique est active au stade 2-cellules. A ce stade, les embryons expriment de l'adn micro-injecte et utilisent efficacement certains promoteurs dans des essais a court terme. Cette capacite apparait a la fin du stade 1-cellule, et est contemporaine, dans ces ufs, de l'activation mineure du genome. Avant ce stade l'arn micro-injecte est efficacement traduit. Il existerait apres la fecondation, un blocage transcriptionnel, leve independamment du clivage de l'uf et de la formation du noyau zygotique mais, dependant de l'age de l'uf. Une etude similaire menee chez le lapin a montre l'existence d'un meme type de blocage. La micro-injection du gene lacz sous controle de differents promoteurs a permis de degager des caracteristiques de la specificite transcriptionnelle des embryons (souris et lapin). Ces caracteristiques transcriptionnelles ont ete aussi observees dans les ovocytes et au stade 4-cellules chez la souris; elles rappellent celles des cellules ec et es. L'expression du gene lacz dirige par le promoteur du vih-1 a ete comparee au stade 2-cellules, en expression transitoire et a l'etat integre (souris transgenique). L'expression detectee en expression transitoire n'est plus observee chez l'embryon transgenique, sauf apres activation par les uv et/ou la mise en culture. Dans ce cas l'expression est contemporaine de l'activation mineure du genome

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50

Díaz, de Ståhl Teresita. "Fcγ Receptors in the Immune Response." Doctoral thesis, Uppsala University, Department of Genetics and Pathology, 2001. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-1545.

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Circulating immune complexes play an important role in the modulation of antibody responses and in the pathogenesis of immune diseases. This thesis deals with the in vivo regulatory properties of antibodies and their specific Fc receptors.

The immunosuppressive function of IgG is used clinically, to prevent rhesus-negative women from becoming sensitized to rhesus-positive erythrocytes from the fetus. The mechanism behind this regulation is poorly understood but involvement of a receptor for IgG, FcγRII, has been suggested. It is shown in this thesis that IgG and also IgE induce immunosuppression against sheep erythrocytes to a similar extent both in mice lacking all the known Fc receptors as in wild-type animals. These findings imply that antibody-mediated suppression of humoral responses against particulate antigens is Fc-independent and that the major operating mechanism is masking of epitopes.

Immunization with soluble antigens in complex with specific IgG leads to an augmentation of antibody production. The cellular mechanism behind this control is examined here and it is found that the capture of IgG2a immune complexes by a bone marrow-derived cell expressing FcγRI (and FcγRIII) is essential. An analysis of the ability of IgG3 to mediate this regulation indicated that, in contrast, this subclass of IgG augments antibody responses independently of FcγRI (and FcγRIII). These findings suggest that distinct mechanisms mediate the enhancing effect of different subclasses of antibodies.

Finally, the contribution of FcγRIII was studied in the development of collagen-induced arthritis (CIA), an animal model for rheumatoid arthritis in humans. It was discovered that while DBA/1 wild-type control mice frequently developed severe CIA, with high incidence, FcγRIII-deficient mice were almost completely protected, indicating a crucial role for FcγRIII in CIA.

The results presented here help to understand how immune complexes regulate immune responses in vivo and show that Fc receptors for IgG, if involved, could be new targets for the treatment of immune complex-related disorders.

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Dissertations / Theses on the topic 'TRANSGENIC ANIMAL'

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