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

Neurobiol Dis. 1995 Jun;2(3):129-38. doi: 10.1006/nbdi.1995.0014.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Base Sequence
  • Blotting, Northern
  • Brain Diseases / genetics*
  • Cloning, Molecular*
  • DNA, Complementary
  • Gene Expression*
  • Glutamine / genetics
  • Huntington Disease / genetics
  • In Situ Hybridization
  • Molecular Sequence Data
  • Point Mutation
  • RNA, Messenger
  • Rats
  • Rats, Sprague-Dawley
  • Trinucleotide Repeats

Substances

  • DNA, Complementary
  • RNA, Messenger
  • Glutamine

Associated data

  • GENBANK/U31777