Progressive CAG expansion in the brain of a novel R6/1-89Q mouse model of Huntington's disease with delayed phenotypic onset.
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.
Vatsavayai
Sarat C
SC
Huntington's Disease Research Forum, Department of Biological Sciences, The Open University, Walton Hall, Milton Keynes, UK.
Dallérac
Glenn M
GM
Milnerwood
Austen J
AJ
Cummings
Damian M
DM
Rezaie
Payam
P
Murphy
Kerry P S J
KP
Hirst
Mark C
MC
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
C506812:Htt protein, mouse; D000071058:Huntingtin Protein; D009419:Nerve Tissue Proteins; D009687:Nuclear Proteins