CELLULAR-LOCALIZATION OF THE HUNTINGTONS-DISEASE PROTEIN AND DISCRIMINATION OF THE NORMAL AND MUTATED FORM

Huntington's disease (HD) results from the expansion of a polyglutamin e encoding CAG repeat in a gene of unknown function. The wide expressi on of this transcript does not correlate with the pattern of neuropath ology in HD. To study the HD gene product (huntingtin), we have develo ped monoclonal antibodies raised against four different regions of the protein. On western blots, these monoclonals detect the similar to 35 0 kD huntingtin protein in various human cell lines and in neural and non-neural rodent tissues. In cell lines from HD patients, a doublet p rotein is detected corresponding to the mutated and normal huntingtin. Immunohistochemical studies in the human brain using two of these ant ibodies detects the huntingtin in perikarya of some neurons, neuropile s, varicosities and as punctate staining likely to be nerve endings.