Progressive CAG expansion in the brain of a novel R6/1-89Q mouse model of Huntington's disease with delayed phenotypic onset

Vatsavayai, Sarat C.; Dallerac, Glenn M.; Milnerwood, Austen J.; Cummings, Damian M.; Rezaie, Payam; Murphy, Kerry P.S.J. and Hirst, Mark C. (2007). Progressive CAG expansion in the brain of a novel R6/1-89Q mouse model of Huntington's disease with delayed phenotypic onset. Brain Research Bulletin, 72(2-3) pp. 98–102.

DOI: https://doi.org/10.1016/j.brainresbull.2006.10.015

Abstract

Transgenic models representing Huntington's disease (HD) have proved useful for understanding the cascade of molecular events leading to the disease. We report an initial characterisation of a novel transgenic mouse model derived from a spontaneous truncation event within the R6/1 transgene. The transgene is widely expressed, carries 89 CAG repeats and the animals exhibit a significantly milder neurological phenotype with delayed onset compared to R6/1. Moreover, we report evidence of progressive somatic CAG expansions in the brain starting at an early age before an overt phenotype has developed. This novel line shares a common genetic ancestry with R6/1, differing only in CAG repeat number, and therefore, provides an additional tool with which to examine early molecular and neurophysiological changes in HD.