As early as 9 weeks of age heterozygous mice exhibit cytoplasmic aggregation foci of HTT (huntingtin) protein, and by 20 weeks of age exhibit striatal neuronal intranuclear inclusions (NIIs). By 40 weeks of age, the striatal aggregation foci are perinuclear and exhibit increased immunoreactivity for ubiquitin and autophagosome marker LC3. Heterozygotes exhibit impaired balance and diminished motor coordination by 50 weeks of age, and abnormal gait by 60 weeks. By 80 weeks of age, heterozygotes display loss of grip strength, striatal and cortical astrogliosis, and a loss of approximately 50% of striatal dopamine receptor binding with increased glial fibrillary acidic protein immunoreactivity. Increased glial fibrillary acidic protein immunoreactivity is present in the striatum and ubiquititin- and huntingtin-positive neuronal intranuclear inclusions (NIIs) are detected throughout the dorsal striatum, nucleus accumbens and to a lesser extent other regions of the brain. Mutant CAG/polyQ repeat expression is slightly lower than wildtype levels as detected by Western blot analysis and qRTPCR of brain tissue. Mutant mice may be noticeably smaller than wild-type littermates. Mice homozygous for the targeted allele are viable and fertile. Onset of symptoms occurs earlier for homozygotes than for heterozygotes. Motor deficits are detected in homozygotes as early as 20 weeks of age. After 30 weeks of age mutant mice may become infertile.
This strain is one of a set of different CAG/polyQ repeat length mutants derived from HdhQ150 (STOCK no. 004595 ). The set includes, STOCK numbers: 016521, 016522, 016523, 016524, 016525.
