cDNA cloning and characterization of an Atrophin-1 (DRPLA disease gene)-related protein

Dentatorubral and pallidoluylsian atrophy (DRPLA) is a progressive neurological disorder characterized by neuronal degeneration, especially in the cerebellar dentate nucleus. DRPLA is caused by an unstable expansion 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 member of the atrophin-1 gene family by screening rat cDNA libraries. The 1006-amino-acid product of this gene, which we have termed rat atrophin related protein(rARP), does not contain a glutamine repeat, but it does contain two regions of alternating acidic and basic amino residues similar to those found in atrophin-1. rARP is widely expressed as both a 7.4- and a 9.4-kb message, with enrichment in cerebellum and testis. Like atrophin-1, the rARP in vitro translation product migrates more 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.