HTT and Huntington disease: Consistent with genetic studies in distinct CAG-expansion neurodegenerative disorders and CAG knock-in mice that replicate the HD mutation, the mechanism that triggers the disease process that leads to the characteristic vulnerability of striatal neurons in HD is thought to involve a novel gain of function that is conferred on mutant huntingtin by the expanded polyglutamine segment (Gusella and MacDonald, 2000; Nucifora et al., 2001; Trettel et al., 2000).