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

Scott J. Loev, Russell Louis Margolis, W. Scott Young, Shi Hua Li, Gabriele Schilling, Roxann G. Ashworth, Christopher A Ross

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Pages (from-to)129-138
Number of pages10
JournalNeurobiology of Disease
Volume2
Issue number3
StatePublished - 1995

Fingerprint

Progressive Myoclonic Epilepsy
Glutamine
Organism Cloning
Complementary DNA
Genes
Proline
Trinucleotide Repeats
Huntington Disease
Base Pairing
Serine
Open Reading Frames
In Situ Hybridization
Amino Acid Sequence
Reference Values
Gene Expression
Messenger RNA
Brain
Proteins

Keywords

  • Dentato-rubral and pallidoluysian atrophy
  • Expansion mutation
  • Glutamine
  • Huntington's disease
  • Neurodegeneration
  • Trinucleotide repeat

ASJC Scopus subject areas

  • Neurology

Cite this

Loev, S. J., Margolis, R. L., Young, W. S., Li, S. H., Schilling, G., Ashworth, R. G., & Ross, C. A. (1995). Cloning and expression of the rat atrophin-I (DRPLA disease gene) homologue. Neurobiology of Disease, 2(3), 129-138.

Cloning and expression of the rat atrophin-I (DRPLA disease gene) homologue. / Loev, Scott J.; Margolis, Russell Louis; Young, W. Scott; Li, Shi Hua; Schilling, Gabriele; Ashworth, Roxann G.; Ross, Christopher A.

In: Neurobiology of Disease, Vol. 2, No. 3, 1995, p. 129-138.

Research output: Contribution to journalArticle

Loev, SJ, Margolis, RL, Young, WS, Li, SH, Schilling, G, Ashworth, RG & Ross, CA 1995, 'Cloning and expression of the rat atrophin-I (DRPLA disease gene) homologue', Neurobiology of Disease, vol. 2, no. 3, pp. 129-138.
Loev SJ, Margolis RL, Young WS, Li SH, Schilling G, Ashworth RG et al. Cloning and expression of the rat atrophin-I (DRPLA disease gene) homologue. Neurobiology of Disease. 1995;2(3):129-138.
Loev, Scott J. ; Margolis, Russell Louis ; Young, W. Scott ; Li, Shi Hua ; Schilling, Gabriele ; Ashworth, Roxann G. ; Ross, Christopher A. / Cloning and expression of the rat atrophin-I (DRPLA disease gene) homologue. In: Neurobiology of Disease. 1995 ; Vol. 2, No. 3. pp. 129-138.
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