Stock No. 027432 was formerly associated with CHDI Foundation colony Stock No. 370231 [CHDI-81001013].
 Huntington's disease (HD) is an autosomally dominant, fatal neurodegenerative disorder characterized by uncontrolled movements, psychiatric disturbances and cognitive impairment. HD is caused by an unstable trinucleotide (polyglutamine) repeat expansion in the huntingtin gene (HTT; HD or Hdh). YAC128 transgenic mice from founder line 53 express the human huntingtin protein containing a glutamine repeat expansion. Original characterization (on FVB genetic background) reported that founder line 53 integrated the most copies of the transgene and had the highest levels of protein expression (75% of endogenous levels) as determined by densitometric analysis. Additionally, individual transgene copies stably expressed HTT with 100 glutamine repeats or HTT with 126 glutamine repeats (see more recent data below). 
 Stock No. 027432: The C57BL/6-congenic YAC128 transgenic mouse line is called B6.YAC128. Hemizygous mice are viable and fertile, with hypoactivity (~8-32 weeks of age), abnormal gait, and motor impairment (rotarod deficit ~4 weeks of age). B6.YAC128 exhibit weight gain (which can confound motor endpoint evaluation) evident in females from ~8 weeks of age and in males from ~16 weeks of age. Overall survival is similar to wildtype (noncarrier) mice up to 1 year of age or longer. The B6.YAC128 mice are not further characterized to date (April 2014). As of 2016 (total N10 or more generations onto C57BL/6), our Stock No. 027432 live colony had shown stable inheritance of two glutamine repeat sizes (~119-121 and ~94-96). 
 While genetic background may lead to variations in disease severity/progression, these B6.YAC128 mice may exhibit a phenotype similar to that of YAC128 mice from the same founder line on the FVB/N genetic background. Those FVB.YAC128 transgenic mice are described and available as Stock No. <a href="https://www.jax.org/strain/004938">004938</a>. Briefly, FVB.YAC128 mice exhibit a progressive neurological phenotype that mimics many of the pathophysiological features of HD. This includes hyperkinesis, abnormal gait, motor impairment, neuronal cell loss, neurodegeneration and nuclear huntingtin aggregate inclusions in striatal neurons.
 Importantly, if a behavioral testing battery includes cognitive tests that require the animals to use visual cues, these B6.YAC128 mice may be preferred over the FVB.YAC128 mice (as FVB/N-congenic background imparts the Pde6brd1 mutation causing retinal degeneration and blindness at an early age). In addition, the relatively high aggression levels in FVB/N mice, especially males, may cause problems during experiments that require long-term group-housing. Conversely, mice on the C57BL/6-congenic background may exhibit age-related hearing loss and become deaf to certain frequencies. 
 This Huntington's disease mouse model is available by way of a collaborative effort between CHDI Foundation, Dr. Michael R. Hayden (University of British Columbia) and The Jackson Laboratory.

The C57BL/6-congenic YAC128 transgenic mouse line expresses multiple copies of a full-length human huntingtin gene (HTT; HD or Hdh) modified in exon 1 to have a glutamine repeat expansion (composed primarily of CAG codons but also containing 9 interspersed CAA codons). Individual transgene copies stably express HTT with 100 glutamine repeats or HTT with 126 glutamine repeats. These B6.YAC128 mice may be useful for studying Huntington's disease on a defined congenic background (without blindness), as well as for exploring the effect of interrupted CAG tracts versus non-interrupted CAG tracts on somatic instability and RNA structure mechanisms in HD pathophysiology.

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