The Experts below are selected from a list of 29313 Experts worldwide ranked by ideXlab platform
F Chen - One of the best experts on this subject based on the ideXlab platform.
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Transgenic Animal models of Alzheimer's disease and related disorders: histopathology, behavior and therapy
Molecular Psychiatry, 2004Co-Authors: Jurgen Gotz, J R Streffer, D David, A Schild, F Hoerndli, L Pennanen, P Kurosinski, F ChenAbstract:Alzheimer's disease (AD) is a devastating neurodegenerative disease that affects more than 15 million people worldwide. Within the next generation, these numbers will more than double. To assist in the elucidation of pathogenic mechanisms of AD and related disorders, such as frontotemporal dementia (FTDP-17), genetically modified mice, flies, fish and worms were developed, which reproduce aspects of the human histopathology, such as β -amyloid-containing plaques and tau-containing neurofibrillary tangles (NFT). In mice, the tau pathology caused selective behavioral impairment, depending on the distribution of the tau aggregates in the brain. β -Amyloid induced an increase in the numbers of NFT, whereas the opposite was not observed in mice. In β -amyloid-producing Transgenic mice, memory impairment was associated with increased levels of β -amyloid. Active and passive β -amyloid-directed immunization caused the removal of β -amyloid plaques and restored memory functions. These findings have since been translated to human therapy. This review aims to discuss the suitability and limitations of the various Animal models and their contribution to an understanding of the pathophysiology of AD and related disorders.
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Transgenic Animal models of alzheimer s disease and related disorders histopathology behavior and therapy
Molecular Psychiatry, 2004Co-Authors: Juergen Gotz, J R Streffer, A Schild, F Hoerndli, L Pennanen, P Kurosinski, Della C David, F ChenAbstract:Alzheimer's disease (AD) is a devastating neurodegenerative disease that affects more than 15 million people worldwide. Within the next generation, these numbers will more than double. To assist in the elucidation of pathogenic mechanisms of AD and related disorders, such as frontotemporal dementia (FTDP-17), genetically modified mice, flies, fish and worms were developed, which reproduce aspects of the human histopathology, such as beta-amyloid-containing plaques and tau-containing neurofibrillary tangles (NFT). In mice, the tau pathology caused selective behavioral impairment, depending on the distribution of the tau aggregates in the brain. Beta-amyloid induced an increase in the numbers of NFT, whereas the opposite was not observed in mice. In beta-amyloid-producing Transgenic mice, memory impairment was associated with increased levels of beta-amyloid. Active and passive beta-amyloid-directed immunization caused the removal of beta-amyloid plaques and restored memory functions. These findings have since been translated to human therapy. This review aims to discuss the suitability and limitations of the various Animal models and their contribution to an understanding of the pathophysiology of AD and related disorders.
Jurgen Gotz - One of the best experts on this subject based on the ideXlab platform.
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a decade of tau Transgenic Animal models and beyond
Brain Pathology, 2007Co-Authors: Jurgen Gotz, Natasha Deters, Amy Doldissen, Laita Bokhari, Andreas Wiesner, Nicole Schonrock, Lars M IttnerAbstract:The first tau Transgenic mouse model was established more than a decade ago. Since then, much has been learned about the role of tau in Alzheimer's disease and related disorders. Animal models, both in vertebrates and invertebrates, were significantly improved and refined as a result of the identification of pathogenic mutations in Tau in human cases of frontotemporal dementia. They have been instrumental for dissecting the cross-talk between tau and the second hallmark lesion of Alzheimer's disease, the Aβ peptide-containing amyloid plaque. We discuss how the tau models have been used to unravel the pathophysiology of Alzheimer's disease, to search for disease modifiers and to develop novel treatment strategies. While tau has received less attention than Aβ, it is rapidly acquiring a more prominent position and the emerging view is one of a synergistic action of Aβ and tau in Alzheimer's disease. Moreover, the existence of a number of neurodegenerative diseases with tau pathology in the absence of extracellular deposits underscores the relevance of research on tau.
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Transgenic Animal models of Alzheimer's disease and related disorders: histopathology, behavior and therapy
Molecular Psychiatry, 2004Co-Authors: Jurgen Gotz, J R Streffer, D David, A Schild, F Hoerndli, L Pennanen, P Kurosinski, F ChenAbstract:Alzheimer's disease (AD) is a devastating neurodegenerative disease that affects more than 15 million people worldwide. Within the next generation, these numbers will more than double. To assist in the elucidation of pathogenic mechanisms of AD and related disorders, such as frontotemporal dementia (FTDP-17), genetically modified mice, flies, fish and worms were developed, which reproduce aspects of the human histopathology, such as β -amyloid-containing plaques and tau-containing neurofibrillary tangles (NFT). In mice, the tau pathology caused selective behavioral impairment, depending on the distribution of the tau aggregates in the brain. β -Amyloid induced an increase in the numbers of NFT, whereas the opposite was not observed in mice. In β -amyloid-producing Transgenic mice, memory impairment was associated with increased levels of β -amyloid. Active and passive β -amyloid-directed immunization caused the removal of β -amyloid plaques and restored memory functions. These findings have since been translated to human therapy. This review aims to discuss the suitability and limitations of the various Animal models and their contribution to an understanding of the pathophysiology of AD and related disorders.
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tau and Transgenic Animal models
Brain Research Reviews, 2001Co-Authors: Jurgen GotzAbstract:Abstract Advances in genetics and Transgenic approaches have a continuous impact on our understanding of Alzheimer’s disease (AD) and related disorders, especially as aspects of the histopathology and neurodegeneration can be reproduced in Animal models. AD is characterized by extracellular Aβ peptide-containing plaques and neurofibrillary aggregates of hyperphosphorylated isoforms of microtubule-associated protein tau. A causal link between Aβ production, neurodegeneration and dementia has been established with the identification of familial forms of AD which are linked to mutations in the amyloid precursor protein APP, from which the Aβ peptide is derived by proteolysis. No mutations have been identified in the tau gene in AD until today. Tau filament formation, in the absence of Aβ production, is also a feature of several additional neurodegenerative diseases including progressive supranuclear palsy, corticobasal degeneration, Pick’s disease, and frontotemporal dementia with parkinsonism linked to chromosome 17 (FTDP-17). The identification of mutations in the tau gene which are linked to FTDP-17 established that dysfunction of tau can, as well as Aβ formation, lead to neurodegeneration and dementia. In this review, newly recognized cellular functions of tau, and the neuropathology and clinical syndrome of FTDP-17 will be presented, as well as recent advances that have been achieved in studies of Transgenic mice expressing tau and AD-related kinases and phosphatases. These models link neurofibrillary lesion formation to neuronal loss, provide an in vivo model in which therapies can be assessed, and may contribute to determine the relationship between Aβ production and tau pathology.
L M Houdebine - One of the best experts on this subject based on the ideXlab platform.
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Transgenic Animal Production
Biotechnology for Sustainable Agriculture, 2018Co-Authors: L M HoudebineAbstract:Abstract Transgenesis is a potent method to generate new breeds of Animals known as genetically modified Animals (GMAs) or genetically engineered Animals. Transgenesis includes two complementary gene modifications: foreign gene addition to Animal genomes and gene replacement. The precise gene replacement may lead to the addition of an exogenous active gene (knock in) and the specific Animal gene inactivation (knock out). The foreign genes may be transferred into pluripotent cells (mammalian embryonic stem or induced pluripotent stem), or into multipotent cells (chicken embryonic gonad cells) further used to generate chimeric Transgenic Animals. Somatic cells may also be used to generate Transgenic clones. The rate of homologous recombination is markedly enhanced by cleaving locally the two genomic DNA strands using targeted nucleases. The cleaved DNA is then spontaneously and randomly repaired leading to targeted gene knock out. The generation of GMA including farm Animals has thus become easier, cheaper, more precise, and safer. A number of vectors are being designed to optimize the expression of transgenes. Transgenic Animals are being used to study gene mechanism and function, to adapt pig organs to be transferred to humans, to prepare recombinant pharmaceutical proteins in milk and egg white, and to improve breeding and food production.
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Transgenic Animal models in biomedical research
Methods of Molecular Biology, 2007Co-Authors: L M HoudebineAbstract:Transgenic Animals have become a key tool in functional genomics to generate models for human diseases and validate new drugs. Transgenesis includes the addition of foreign genetic information to Animals and specific inhibition of endogenous gene expression. Recently, Animal models provided novel insight and significantly improved our understanding of the initiation and perpetuation of human diseases. Moreover, they are an invaluable tool for target discovery, validation, and production of therapeutic proteins. However, despite the generation of several Transgenic and knockout models, obtaining relevant models still faces several theoretical and technical challenges. Indeed, genes of interest are not always available and gene addition or inactivation sometimes does not allow clear conclusions because of the intrinsic complexity of living organisms or the redundancy of some metabolic pathways. In addition to homologous recombination, endogenous gene expression can be specifically inhibited using several mechanisms such as RNA interference. Here, some Animal models are described to illustrate their importance in biomedical research. Moreover, guidelines for generation of these Animals are presented.
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Transgenic Animal bioreactors
Transgenic Research, 2000Co-Authors: L M HoudebineAbstract:The production of recombinant proteins is one of the major successes of biotechnology. Animal cells are required to synthesize proteins with the appropriate post-translational modifications. Transgenic Animals are being used for this purpose. Milk, egg white, blood, urine, seminal plasma and silk worm cocoon from Transgenic Animals are candidates to be the source of recombinant proteins at an industrial scale. Although the first recombinant protein produced by Transgenic Animals is expected to be in the market in 2000, a certain number of technical problems remain to be solved before the various systems are optimized. Although the generation of Transgenic farm Animals has become recently easier mainly with the technique of Animal cloning using transfected somatic cells as nuclear donor, this point remains a limitation as far as cost is concerned. Numerous experiments carried out for the last 15 years have shown that the expression of the transgene is predictable only to a limited extent. This is clearly due to the fact that the expression vectors are not constructed in an appropriate manner. This undoubtedly comes from the fact that all the signals contained in genes have not yet been identified. Gene constructions thus result sometime in poorly functional expression vectors. One possibility consists in using long genomic DNA fragments contained in YAC or BAC vectors. The other relies on the identification of the major important elements required to obtain a satisfactory transgene expression. These elements include essentially gene insulators, chromatin openers, matrix attached regions, enhancers and introns. A certain number of proteins having complex structures (formed by several subunits, being glycosylated, cleaved, carboxylated...) have been obtained at levels sufficient for an industrial exploitation. In other cases, the mammary cellular machinery seems insufficient to promote all the post-translational modifications. The addition of genes coding for enzymes involved in protein maturation has been envisaged and successfully performed in one case. Furin gene expressed specifically in the mammary gland proved to able to cleave native human protein C with good efficiency. In a certain number of cases, the recombinant proteins produced in milk have deleterious effects on the mammary gland function or in the Animals themselves. This comes independently from ectopic expression of the transgenes and from the transfer of the recombinant proteins from milk to blood. One possibility to eliminate or reduce these side-effects may be to use systems inducible by an exogenous molecule such as tetracycline allowing the transgene to be expressed only during lactation and strictly in the mammary gland. The purification of recombinant proteins from milk is generally not particularly difficult. This may not be the case, however, when the endogenous proteins such as serum albumin or antibodies are abundantly present in milk. This problem may be still more crucial if proteins are produced in blood. Among the biological contaminants potentially present in the recombinant proteins prepared from Transgenic Animals, prions are certainly those raising the major concern. The selection of Animals chosen to generate Transgenics on one hand and the elimination of the potentially contaminated Animals, thanks to recently defined quite sensitive tests may reduce the risk to an extremely low level. The available techniques to produce pharmaceutical proteins in milk can be used as well to optimize milk composition of farm Animals, to add nutriceuticals in milk and potentially to reduce or even eliminate some mammary infectious diseases.
P Kurosinski - One of the best experts on this subject based on the ideXlab platform.
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Transgenic Animal models of Alzheimer's disease and related disorders: histopathology, behavior and therapy
Molecular Psychiatry, 2004Co-Authors: Jurgen Gotz, J R Streffer, D David, A Schild, F Hoerndli, L Pennanen, P Kurosinski, F ChenAbstract:Alzheimer's disease (AD) is a devastating neurodegenerative disease that affects more than 15 million people worldwide. Within the next generation, these numbers will more than double. To assist in the elucidation of pathogenic mechanisms of AD and related disorders, such as frontotemporal dementia (FTDP-17), genetically modified mice, flies, fish and worms were developed, which reproduce aspects of the human histopathology, such as β -amyloid-containing plaques and tau-containing neurofibrillary tangles (NFT). In mice, the tau pathology caused selective behavioral impairment, depending on the distribution of the tau aggregates in the brain. β -Amyloid induced an increase in the numbers of NFT, whereas the opposite was not observed in mice. In β -amyloid-producing Transgenic mice, memory impairment was associated with increased levels of β -amyloid. Active and passive β -amyloid-directed immunization caused the removal of β -amyloid plaques and restored memory functions. These findings have since been translated to human therapy. This review aims to discuss the suitability and limitations of the various Animal models and their contribution to an understanding of the pathophysiology of AD and related disorders.
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Transgenic Animal models of alzheimer s disease and related disorders histopathology behavior and therapy
Molecular Psychiatry, 2004Co-Authors: Juergen Gotz, J R Streffer, A Schild, F Hoerndli, L Pennanen, P Kurosinski, Della C David, F ChenAbstract:Alzheimer's disease (AD) is a devastating neurodegenerative disease that affects more than 15 million people worldwide. Within the next generation, these numbers will more than double. To assist in the elucidation of pathogenic mechanisms of AD and related disorders, such as frontotemporal dementia (FTDP-17), genetically modified mice, flies, fish and worms were developed, which reproduce aspects of the human histopathology, such as beta-amyloid-containing plaques and tau-containing neurofibrillary tangles (NFT). In mice, the tau pathology caused selective behavioral impairment, depending on the distribution of the tau aggregates in the brain. Beta-amyloid induced an increase in the numbers of NFT, whereas the opposite was not observed in mice. In beta-amyloid-producing Transgenic mice, memory impairment was associated with increased levels of beta-amyloid. Active and passive beta-amyloid-directed immunization caused the removal of beta-amyloid plaques and restored memory functions. These findings have since been translated to human therapy. This review aims to discuss the suitability and limitations of the various Animal models and their contribution to an understanding of the pathophysiology of AD and related disorders.
J R Streffer - One of the best experts on this subject based on the ideXlab platform.
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Transgenic Animal models of Alzheimer's disease and related disorders: histopathology, behavior and therapy
Molecular Psychiatry, 2004Co-Authors: Jurgen Gotz, J R Streffer, D David, A Schild, F Hoerndli, L Pennanen, P Kurosinski, F ChenAbstract:Alzheimer's disease (AD) is a devastating neurodegenerative disease that affects more than 15 million people worldwide. Within the next generation, these numbers will more than double. To assist in the elucidation of pathogenic mechanisms of AD and related disorders, such as frontotemporal dementia (FTDP-17), genetically modified mice, flies, fish and worms were developed, which reproduce aspects of the human histopathology, such as β -amyloid-containing plaques and tau-containing neurofibrillary tangles (NFT). In mice, the tau pathology caused selective behavioral impairment, depending on the distribution of the tau aggregates in the brain. β -Amyloid induced an increase in the numbers of NFT, whereas the opposite was not observed in mice. In β -amyloid-producing Transgenic mice, memory impairment was associated with increased levels of β -amyloid. Active and passive β -amyloid-directed immunization caused the removal of β -amyloid plaques and restored memory functions. These findings have since been translated to human therapy. This review aims to discuss the suitability and limitations of the various Animal models and their contribution to an understanding of the pathophysiology of AD and related disorders.
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Transgenic Animal models of alzheimer s disease and related disorders histopathology behavior and therapy
Molecular Psychiatry, 2004Co-Authors: Juergen Gotz, J R Streffer, A Schild, F Hoerndli, L Pennanen, P Kurosinski, Della C David, F ChenAbstract:Alzheimer's disease (AD) is a devastating neurodegenerative disease that affects more than 15 million people worldwide. Within the next generation, these numbers will more than double. To assist in the elucidation of pathogenic mechanisms of AD and related disorders, such as frontotemporal dementia (FTDP-17), genetically modified mice, flies, fish and worms were developed, which reproduce aspects of the human histopathology, such as beta-amyloid-containing plaques and tau-containing neurofibrillary tangles (NFT). In mice, the tau pathology caused selective behavioral impairment, depending on the distribution of the tau aggregates in the brain. Beta-amyloid induced an increase in the numbers of NFT, whereas the opposite was not observed in mice. In beta-amyloid-producing Transgenic mice, memory impairment was associated with increased levels of beta-amyloid. Active and passive beta-amyloid-directed immunization caused the removal of beta-amyloid plaques and restored memory functions. These findings have since been translated to human therapy. This review aims to discuss the suitability and limitations of the various Animal models and their contribution to an understanding of the pathophysiology of AD and related disorders.
