title: Progressive CAG expansion in the brain of a novel R6/1-89Q mouse model of Huntington's disease with delayed phenotypic onset.
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.
authors.affiliation: Huntington's Disease Research Forum, Department of Biological Sciences, The Open University, Walton Hall, Milton Keynes, UK.
authors.forename: Sarat C
authors.initials: SC
authors.lastname: Vatsavayai
authors.forename: Glenn M
authors.initials: GM
authors.lastname: Dallérac
authors.forename: Austen J
authors.initials: AJ
authors.lastname: Milnerwood
authors.forename: Damian M
authors.initials: DM
authors.lastname: Cummings
authors.forename: Payam
authors.initials: P
authors.lastname: Rezaie
authors.forename: Kerry P S J
authors.initials: KP
authors.lastname: Murphy
authors.forename: Mark C
authors.initials: MC
authors.lastname: Hirst
mesh_terms: D000818:Animals; D001921:Brain / Q000378:metabolism* / Q000473:pathology; D004195:Disease Models, Animal; D005838:Genotype; D000071058:Huntingtin Protein; D006816:Huntington Disease / Q000235:genetics*; D007150:Immunohistochemistry; D051379:Mice; D008822:Mice, Transgenic; D009419:Nerve Tissue Proteins / Q000235:genetics; D009687:Nuclear Proteins / Q000235:genetics; D010641:Phenotype; D016133:Polymerase Chain Reaction; D019680:Trinucleotide Repeat Expansion
chemical_list: C506812:Htt protein, mouse; D000071058:Huntingtin Protein; D009419:Nerve Tissue Proteins; D009687:Nuclear Proteins