Cloning and expression of the rat atrophin-I (DRPLA disease gene) homologue

Dentatorubral pallidoluysian atrophy (DRPLA) is a rare, progressive, fatal neuropsychiatric disorder similar to Huntington's disease, caused by an expansion of a CAG trinucleotide repeat encoding glutamine. We have cloned the cDNA of the rat homologue of this gene. The cDNA contains a 3549 base pair open reading frame that is 88.2% identical to the human cDNA, with a predicted amino acid sequence that is 93.6% identical to the human sequence. The consecutive glutamine repeat is only five residues in length (normal. range in human: 7-35 glutamines) and is followed by a polymorphic region of alternating glutamine and proline residues (QQQQQPQPQPQPQQ) The sequence also includes a polymorphic proline repeat, a serine repeat, and a region of alternating acidic and basic residues. Northern analysis and in situ hybridization indicate that the gene is widely expressed as a 4.5 kb mRNA, with a neuronal distribution in the brain. The widespread expression of this gene is consistent with the possibility that DRPLA, like other glutamine repeat diseases, is a result of an abnormality at the protein level.