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

• Published in: Neurobiology of disease Vol. 2; no. 3; pp. 129 - 138
• Main Authors: Loev, Scott J., Margolis, Russell L., Young, W.Scott, Li, Shi-Hua, Schilling, Gabriele, Ashworth, Roxann G., Ross, Christopher A.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01-06-1995; Elsevier
• Subjects: Animals; Base Sequence; Blotting, Northern; Brain Diseases - genetics; Cloning, Molecular; Dentato-rubral and pallidoluysian atrophy; DNA, Complementary; expansion mutation; Gene Expression; glutamine; Glutamine - genetics; Huntington Disease - genetics; Huntington's disease; In Situ Hybridization; Molecular Sequence Data; neurodegeneration; Point Mutation; Rats; Rats, Sprague-Dawley; RNA, Messenger; trinucleotide repeat; Trinucleotide Repeats; neurodegeneration; trinucleotide repeat; Dentato-rubral and pallidoluysian atrophy; expansion mutation; glutamine; Huntington's disease
• ISSN: 0969-9961; 1095-953X
• DOI: 10.1006/nbdi.1995.0014

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 andin situhybridization 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.