Newly Validated Q175 Knock-in Model Better Indicator of Huntington’s Disease Condition in Humans
Jun 08 2012
Huntington's disease (HD) is an autosomal neurodegenerative disorder, characterized by severe behavioral, cognitive and motor deficits. Several mouse models, including the R6/2 mouse, which expresses a truncated fragment of mHTT, have been generated to examine the pathogenesis of the disease in an effort to develop novel treatment options. The newly validated Q175 knock-in mouse, however, carries the mutation in its appropriate genomic and protein context, making it, mechanistically, the most true-to-life model of the human condition.
Charles River Discovery Research Services has licensed and validated the Q175 knock-in mouse model, a new tool for researchers investigating the effects of HD therapeutics. This model is a counterpart to the widely used R6/2 mouse line, which demonstrates very fast progression of HD-like symptoms. In contrast, the Q175 mouse develops symptoms early, and with slower progression, allowing ample time to observe the early events triggered by the mutation. Full manifestation of HD-like motor deficits and brain atrophy is apparent in homozygote mice from 3 months and in heterozygote littermates by 4 to 8 months of age. The robustness, gene dose-dependency, progression and early-onset alterations in the Q175 pathogenesis provide researchers with a longer window to detect chronic compound administration effects. Charles River’s mouse efficacy test paradigm includes behavior and cognition, in vivo magnetic resonance imaging (MRI) for brain volumetry and magnetic resonance spectroscopy (MRS) for brain metabolites. Additional testing services are described below.
Behavioral and Cognitive Tests for Huntington’s Disease
Motor Deficits
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Open Field Test
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Rear Climbing
Cognitive Deficits
Imaging Tools
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In vivo MRI Brain Volumetry Measurement of the Striatum, Cortex and Whole Brain
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In vivo 1H-MRS of the Striatum Metabolic Profile
Biomarkers
For more information about facilitating your Huntington’s disease study with Charles River’s Q175 knock-in model, please contact us at askcharlesriver@crl.com.