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

Neurobiology of Disease

Russell L. Margolis¹  Christopher A. Ross¹  W.Scott Young²  Shi-Hua Li³  Gabriele Schilling⁴  Roxann G. Ashworth⁵  Scott J. Loev⁵ 

[1] Laboratory of Cell Biology, National Institute of Mental Health, Bethesda, U.S.A.;Laboratory of Molecular Neurobiology, Department of Medical Genetics, Johns Hopkins University School of Medicine, Baltimore, U.S.A.;Laboratory of Molecular Neurobiology, Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, U.S.A.;Laboratory of Molecular Neurobiology, Program in Cellular and Molecular Medicine, Johns Hopkins University School of Medicine, Baltimore, U.S.A.;Laboratory of Molecular Neurobiology, Department of Psychiatry, Johns Hopkins University School of Medicine, Baltimore, U.S.A.;

关键词: Dentato-rubral and pallidoluysian atrophy;    expansion mutation;    glutamine;    Huntington's disease;    trinucleotide repeat;    neurodegeneration;   

DOI  :  

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown