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To characterize this model further, we have performed behavioral and neuropathological analyses that provide a foundation for the use of R6\/2 mice in preclinical therapeutic trials. Behavioral analyses of the R6\/2 mouse reveal age\u2010related impairments in dystonic movements, motor performance, grip strength, and body weight that progressively worsen until death. Significant neuropathological sequela, identified as increasing marked reductions in brain weight, are present from 30 days, whereas decreased brain volume is present from 60 days and decreased neostriatal volume and striatal neuron area, with a concomitant reduction in striatal neuron number, are present at 90 days of age. Huntingtin\u2010positive aggregates are present at postnatal day 1 and increase in number and size with age. Our findings suggest that the R6\/2 HD model exhibits a progressive HD\u2010like behavioral and neuropathological phenotype that more closely corresponds to human HD than previously believed, providing further assurance that the R6\/2 mouse is an appropriate model for testing potential therapies for HD. J. Comp. Neurol. 490:354\u2013370, 2005. \u00a9 2005 Wiley\u2010Liss, Inc.<\/jats:p>","DOI":"10.1002\/cne.20680","type":"journal-article","created":{"date-parts":[[2005,8,26]],"date-time":"2005-08-26T17:47:13Z","timestamp":1125078433000},"page":"354-370","source":"Crossref","is-referenced-by-count":209,"title":["Chronology of behavioral symptoms and neuropathological sequela in R6\/2 Huntington's disease transgenic mice"],"prefix":"10.1002","volume":"490","author":[{"given":"Edward C.","family":"Stack","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James K.","family":"Kubilus","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karen","family":"Smith","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kerry","family":"Cormier","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steven 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