Huntington’s disease (HD) is an autosomal dominant neurodegeneration which is associated with an expanded CAG repeat in a large gene on chromosome 4p. The protein product of the gene, huntingtin, thus contains an expanded glutamine tract close to its N-terminus. Although the genetic lesion was defined in 1993 (Huntington’s disease collaborative research group, 1993) neither the normal nor pathological function of huntingtin has been defined. Despite the widespread expression of the HD gene in effectively all cell types examined (DiFiglia et al., 1995; Ferrante et al., 1997; Gutekunst et al., 1995; Kosinski et al., 1997) the initial pathology of HD is restricted and specific populations of neurons in the striatum are vulnerable (Vonsattel et al., 1985). The neurons which die first are the medium spiny projection neurons in the caudate and putamen, and those most vulnerable are the enkephalin-containing, dopamine D2 expressing neurons projecting to the globus pallidus pars externa (GPe) (Albin et al., 1990; 1992). The death of neurons is accompanied by extensive reactive gliosis and, at later stages of disease, atrophy occurs in other regions of the basal ganglia and elsewhere with brain weight at death significantly reduced compared to controls (Vonsattel et al., 1985)
