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Transgenic rat model of Huntington's disease

Item Type:Article
Title:Transgenic rat model of Huntington's disease
Creators Name:von Hoersten, S. and Schmitt, I. and Nguyen, H.P. and Holzmann, C. and Schmidt, T. and Walther, T. and Bader, M. and Pabst, R. and Kobbe, P. and Krotova, J. and Stiller, D. and Kask, A. and Vaarmann, A. and Rathke-Hartlieb, S. and Schulz, J.B. and Grasshoff, U. and Bauer, I. and Vieira-Saecker, A.M.M. and Paul, M. and Jones, L. and Lindenberg, K.S. and Landwehrmeyer, B. and Bauer, A. and Li, X.J. and Riess, O.
Abstract:Huntington's disease (HD) is a late manifesting neurodegenerative disorder in humans caused by an expansion of a CAG trinucleotide repeat of more than 39 units in a gene of unknown function. Several mouse models have been reported which show rapid progression of a phenotype leading to death within 3-5 months (transgenic models) resembling the rare juvenile course of HD (Westphal variant) or which do not present with any symptoms (knock-in mice). Owing to the small size of the brain, mice are not suitable for repetitive in vivo imaging studies. Also, rapid progression of the disease in the transgenic models limits their usefulness for neurotransplantation. We therefore generated a rat model transgenic of HD, which carries a truncated huntingtin cDNA fragment with 51 CAG repeats under control of the native rat huntingtin promoter. This is the first transgenic rat model of a neurodegenerative disorder of the brain. These rats exhibit adult-onset neurological phenotypes with reduced anxiety, cognitive impairments, and slowly progressive motor dysfunction as well as typical histopathological alterations in the form of neuronal nuclear inclusions in the brain. As in HD patients, in vivo imaging demonstrates striatal shrinkage in magnetic resonance images and a reduced brain glucose metabolism in high-resolution fluor-deoxy-glucose positron emission tomography studies. This model allows longitudinal in vivo imaging studies and is therefore ideally suited for the evaluation of novel therapeutic approaches such as neurotransplantation.
Keywords:Animal Disease Models, Cell Nucleus, Complementary DNA, Disease Progression, Emission-Computed Tomography, Genetic Models, Genetically Modified Animals, Glucose, Huntington Disease, Immunohistochemistry, Magnetic Resonance Imaging, Nerve Tissue Proteins, Neurons, Nuclear Proteins, Phenotype, Promoter Regions, Time Factors, Tissue Distribution, Transgenes, Trinucleotide Repeat Expansion, Tryptophan, Animals, Rats
Source:Human Molecular Genetics
ISSN:0964-6906
Publisher:Oxford University Press (U.K.)
Volume:12
Number:6
Page Range:617-624
Date:15 March 2003
Official Publication:http://hmg.oxfordjournals.org/cgi/content/abstract/12/6/617
PubMed:View item in PubMed

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