Neuronal aggregates are associated with phenotypic onset in the R6/2 Huntington's disease transgenic mouse.

Huntington's disease (HD) is caused by the expansion of the polyglutamine tract expressed in the huntingtin protein. Data from patients show a strong negative correlation between CAG repeat size and age of disease onset. Recent studies in mixed background C57×CBA R6/2 mice suggest the inverse correlation observed in the human disease may not be replicated in some animal models of HD.

Genetic background modulates behavioral impairments in R6/2 mice and suggests a role for dominant genetic modifiers in Huntington’s disease pathogenesis.

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.

Onset and progression of behavioral and molecular phenotypes in a novel congenic R6/2 line exhibiting intergenerational CAG repeat stability.

In the present study we report on the use of speed congenics to generate a C57BL/6J congenic line of HD-model R6/2 mice carrying 110 CAG repeats, which uniquely exhibits minimal intergenerational instability. We also report the first identification of the R6/2 transgene insertion site. The relatively stable line of 110 CAG R6/2 mice was characterized for the onset of behavioral impairments in motor, cognitive and psychiatric-related phenotypes as well as the progression of disease-related impairments from 4 to 10 weeks of age.