RGD Reference Report - Transgenic rat model of Huntington's disease. - Rat Genome Database

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Transgenic rat model of Huntington's disease.

Authors: von Hörsten, Stephan  Schmitt, Ina  Nguyen, Huu Phuc  Holzmann, Carsten  Schmidt, Thorsten  Walther, Thomas  Bader, Michael  Pabst, Reinhard  Kobbe, Philipp  Krotova, Jana  Stiller, Detlef  Kask, Ants  Vaarmann, Annika  Rathke-Hartlieb, Silvia  Schulz, Jörg B  Grasshoff, Ute  Bauer, Ingrid  Vieira-Saecker, Ana Maria Menezes  Paul, Martin  Jones, Lesley  Lindenberg, Katrin S  Landwehrmeyer, Bernhard  Bauer, Andreas  Li, Xiao-Jiang  Riess, Olaf 
Citation: von Hörsten S, etal., Hum Mol Genet. 2003 Mar 15;12(6):617-24.
RGD ID: 13452381
Pubmed: (View Article at PubMed) PMID:12620967

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.



Disease Annotations    

Phenotype Annotations    

Mammalian Phenotype
Objects Annotated

Genes (Rattus norvegicus)
Htt  (huntingtin)

Genes (Mus musculus)
Htt  (huntingtin)

Genes (Homo sapiens)
HTT  (huntingtin)

Strains
SD-Tg(Htt*)  (NA)


Additional Information