title: Transgenic rat model of Huntington's disease.
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.
authors.affiliation: Department of Functional and Applied Anatomy, Hannover Medical School, Hannover, Germany. hoersten.stephan.von@mh-hannover.de
authors.forename: Stephan
authors.initials: S
authors.lastname: von Hörsten
authors.forename: Ina
authors.initials: I
authors.lastname: Schmitt
authors.forename: Huu Phuc
authors.initials: HP
authors.lastname: Nguyen
authors.forename: Carsten
authors.initials: C
authors.lastname: Holzmann
authors.forename: Thorsten
authors.initials: T
authors.lastname: Schmidt
authors.forename: Thomas
authors.initials: T
authors.lastname: Walther
authors.forename: Michael
authors.initials: M
authors.lastname: Bader
authors.forename: Reinhard
authors.initials: R
authors.lastname: Pabst
authors.forename: Philipp
authors.initials: P
authors.lastname: Kobbe
authors.forename: Jana
authors.initials: J
authors.lastname: Krotova
authors.forename: Detlef
authors.initials: D
authors.lastname: Stiller
authors.forename: Ants
authors.initials: A
authors.lastname: Kask
authors.forename: Annika
authors.initials: A
authors.lastname: Vaarmann
authors.forename: Silvia
authors.initials: S
authors.lastname: Rathke-Hartlieb
authors.forename: Jörg B
authors.initials: JB
authors.lastname: Schulz
authors.forename: Ute
authors.initials: U
authors.lastname: Grasshoff
authors.forename: Ingrid
authors.initials: I
authors.lastname: Bauer
authors.forename: Ana Maria Menezes
authors.initials: AM
authors.lastname: Vieira-Saecker
authors.forename: Martin
authors.initials: M
authors.lastname: Paul
authors.forename: Lesley
authors.initials: L
authors.lastname: Jones
authors.forename: Katrin S
authors.initials: KS
authors.lastname: Lindenberg
authors.forename: Bernhard
authors.initials: B
authors.lastname: Landwehrmeyer
authors.forename: Andreas
authors.initials: A
authors.lastname: Bauer
authors.forename: Xiao-Jiang
authors.initials: XJ
authors.lastname: Li
authors.forename: Olaf
authors.initials: O
authors.lastname: Riess
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified; D002467:Cell Nucleus / Q000378:metabolism; D018076:DNA, Complementary / Q000378:metabolism; D004195:Disease Models, Animal; D018450:Disease Progression; D005947:Glucose / Q000378:metabolism; D000071058:Huntingtin Protein; D006816:Huntington Disease / Q000235:genetics* / Q000473:pathology*; D007150:Immunohistochemistry; D008279:Magnetic Resonance Imaging; D008957:Models, Genetic; D009419:Nerve Tissue Proteins / Q000235:genetics* / Q000378:metabolism; D009474:Neurons / Q000378:metabolism; D009687:Nuclear Proteins / Q000235:genetics* / Q000378:metabolism; D010641:Phenotype; D011401:Promoter Regions, Genetic; D051381:Rats; D013997:Time Factors; D014018:Tissue Distribution; D014055:Tomography, Emission-Computed; D019076:Transgenes; D019680:Trinucleotide Repeat Expansion; D014364:Tryptophan / Q000378:metabolism
chemical_list: D018076:DNA, Complementary; C499524:Htt protein, rat; D000071058:Huntingtin Protein; D009419:Nerve Tissue Proteins; D009687:Nuclear Proteins; D014364:Tryptophan; D005947:Glucose