MACHADO-JOSEPH-DISEASE GENE-PRODUCT IDENTIFIED IN LYMPHOCYTES AND BRAIN

Machado-Joseph disease (MJD) is associated with the expansion of an un stable CAG repeat. The existence of an abnormal gene product in MJD wa s previously suggested with the expanded polyglutamine stretch-specifi c antibody. However, the product of the normal allele has not previous ly been identified. We generated monoclonal antibodies against the fus ion protein (codon 225-310) of the MJD gene product and then identifie d the MJD1 gene product in normal lymphoblastoid cells as a approximat e to 50-kDa protein by immunoblot analysis. The electrophoretic mobili ty differences among the normal allele products corresponds to the mol ecular size difference produced by the polyglutamine stretch and the p olymorphism at the C-terminus. Moreover, abnormal immunoreactive bands which were larger than the normal ones were found as a approximate to 60-kDa protein exclusively in the MJD samples. The cytoplasm and the nuclei of neurons and glial cells were stained by these antibodies wit h immunocytochemistry. As in other CAG repeat diseases, the abnormal a nd normal allele products were almost equally expressed in lymphoblast oid cells and the brain of MJD patients. (C) 1997 Academic Press.