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g.oxfordjournals.org/ D ow nloaded from 2 Accumulation of N-terminal fragments of mutant huntingtin (mHTT) in the cytoplasm, nuclei, and axons of neurons is a hallmark of Huntington's disease (HD), although how these fragments negatively impact neurons remains unclear. We followed the distribution of mHTT in the striata of transgenic R6/2-J2 HD mice as their motor function declined. The fraction of cells with diffuse, perinuclear or intranuclear mHTT changed in parallel with decreasing motor function. In transgenic mice, medium spiny neurons (MSNs) that exhibited perinuclear inclusions expressed cell cycle markers typically not seen in the striata of normal mice and thes