| Project/Area Number |
03671142
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| Research Category |
Grant-in-Aid for General Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Research Field |
内分泌・代謝学
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| Research Institution | Nagoya University |
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Principal Investigator |
OISO Yutaka Nagoya Univ. School of Medicine Assistant Prof., 医学部, 助手 (40203707)
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| Co-Investigator(Kenkyū-buntansha) |
ITO Masafumi Nagoya Univ. School of Medicine Medical staff, 医学部, 医員
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| Project Period (FY) |
1991 – 1992
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| Project Status |
Completed (Fiscal Year 1992)
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| Budget Amount *help |
¥2,000,000 (Direct Cost: ¥2,000,000)
Fiscal Year 1992: ¥800,000 (Direct Cost: ¥800,000)
Fiscal Year 1991: ¥1,200,000 (Direct Cost: ¥1,200,000)
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| Keywords | Vasopressin / Neurophysin / Familial Central Diabetes Insipidus / Gene anomaly / Gene Expression / Signal Pepytide / 遺伝子異常 / 遺伝子発現 / バゾプレシン遺伝子 / 蛋白発現 / 糖蛋白 / ニュ-ロフィジン / 転写制御 |
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| Research Abstract |
A transition of G to A at nucleotide position 279 in exon 1 of the vasopressin (VP) gene has been identified in patients with familial central diabetes insipidus. The mutation predicts an amino acid substitution of Thr (ACG) for Ala (GCG) at the COOH-terminus of the signal peptide in prepro VP. Translation in vitro of wild type and mutant mRNAs produced 19 kDa prepro VPs. When traslated in the presence of canine pancreatic rough microsomes, wild type prepro VP was converted to a 21 kDa protein, whereas the mutant mRNA produced proteins of 21 kDa and 23 kDa. NH_2-terminal amino acid sequence analysis revealed that the 21 kDa proteins from the wild type and the mutant were proVPs generated by the proteolytic cleavege of the 19-residue signal peptide and the addition of carbohydrate. Accordingly, mutant preproVP was cleaved at the correct site after Thr-19, but the efficiency of cleavage by signal peptidase was less than 25% that observed for the wild type preproVP, resulting in the formation of a predominant glycosylated but uncleaved 23 kDa product. These data suggest that inefficient processing of preproVP produced by the mutant allele is possibly involved in the pathogenesis of diabetes insipidus in the affected individuals.
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