title: Genetic background modulates behavioral impairments in R6/2 mice and suggests a role for dominant genetic modifiers in Huntington’s disease pathogenesis.
abstract: Variability and modification of the symptoms of Huntington’s disease (HD) are commonly observed in both patient populations and animal models of the disease. Utilizing a stable line of the R6/2 HD mouse model, the present study investigated the role of genetic background in the onset and severity of HD symptoms in a transgenic mouse. R6/2 congenic C57BL/6J and C57BL/6J×DBA/2J F1 (B6D2F1) mice were evaluated for survival and a number of behavioral phenotypes. This study reports that the presence of the DBA/2J allele results in amelioration or exacerbation of several HD-like phenotypes characteristic of the R6/2 mouse model and indicates the presence of dominant genetic modifiers of HD symptoms. This study is the first step in identifying genes that confer natural genetic variation and modify the HD symptoms. This identification may lead to novel targets for treatment and help elucidate the molecular mechanisms of HD pathogenesis.
authors.affiliation: Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA.
authors.forename: Randi-Michelle
authors.initials: RM
authors.lastname: Cowin
authors.forename: Nghiem
authors.initials: N
authors.lastname: Bui
authors.forename: Deanna
authors.initials: D
authors.lastname: Graham
authors.forename: Jennie R
authors.initials: JR
authors.lastname: Green
authors.forename: Lisa A
authors.initials: LA
authors.lastname: Yuva-Paylor
authors.forename: Andreas
authors.initials: A
authors.lastname: Weiss
authors.forename: Richard
authors.initials: R
authors.lastname: Paylor
mesh_terms: D000818:Animals; D001519:Behavior; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D006816:Huntington Disease / Q000235:genetics* / Q000473:pathology / Q000503:physiopathology / Q000523:psychology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D009043:Motor Activity