CDNA CLONING AND CHARACTERIZATION OF AN ATROPHIN-1 (DRPLA DISEASE GENE)-RELATED PROTEIN

Dentatorubral and pallidoluylsian atrophy (DRPLA) is a progressive neu rological disorder characterized by neuronal degeneration, especially in the cerebellar dentate nucleus. DRPLA is caused by an unstable expa nsion of a CAG trinucleotide repeat coding for glutamine in a gene of unknown function, termed atrophin-1, located on chromosome 12. To gain additional understanding of atrophin-1, we have isolated a second mem ber of the atrophin-1 gene family by screening rat cDNA libraries. The 1006-amino-acid product of this gene, which we have termed rat atroph in related protein(rARP), does not contain a glutamine repeat, but it does contain two regions of alternating acidic and basic amino residue s similar to those found in atrophin-1. rARP is widely expressed as bo th a 7.4- and a 9.4-kb message, with enrichment in cerebellum and test is. Like atrophin-1, the rARP in vitro translation product migrates mo re slowly on SDS-polyacrylamide gel electrophoresis than predicted by molecular weight, We conclude that, at least in the rat, polyglutamine is not an essential feature of the atrophin family of genes. (C) 1996 Academic Press, Inc.