1999 Fiscal Year Final Research Report Summary
Molecular Mechanism of Localization of the Mutant Ornithine Transcarbamylase to Mitochondrial Compartment
| Project/Area Number |
09670854
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Pediatrics
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| Research Institution | KURUME UNIVERSITY |
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Principal Investigator |
YOSHINO Makoto Kurume University, School of Medicine, Department of Pediatrics & Child Health, Professor, 医学部, 教授 (40080569)
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| Co-Investigator(Kenkyū-buntansha) |
TOKUNAGA Yasuyuki Kurume University, School of Medicine, Department of Pediatrics & Child Health, Fellow, 医学部, 助手 (60227585)
NISHIYORI Atsushi Kurume University, School of Medicine, Department of Public Health, Assistant Professor, 医学部, 講師 (30218226)
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| Project Period (FY) |
1997 – 1999
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| Keywords | ornithine transcarbamylase / mitochondria / localization |
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| Research Abstract |
1) Research on the transport of wild-type and mutant ornithine transcarbamylase (OTC) into mitochondrial compartment
OTC messenger RNA was isolated from cells transfected with either the wild-type or the R40H OTC cDNA. The mRNA was in vitro-translated with S35, and the labeled OTC was added to isolated rat liver mitochondria. After incubation, incorporation of the label into the protein fractions of various molecular sizes separated on a sephadex column were measured. The incorporation of the label was not reproducible in terms of elution volume and radioactivity in the protein fraction, and further refinements of the experimental conditions were necessary.
2) Prenatal monitoring of a pregnancy at risk for OTC deficiency with neonatal onset
The I261T mutation in the OTC gene was identified in a male neonate who died from hyperammonemic crisis. prenatal diagnosis was done in the successive pregnancy, which revealed that the fetus was female, and that it did not carry the mutant allele. Gene tracking in the family revealed that the mutation was freshly occurred in the mother.
3) Analysis of prognostic factors in male patients with late-onset OTC deficiency
Prognosis of life has been generally poor in male patients with the late-onset OTC to deficiency. To elucidate factors that are concerned with prognosis of life, retrospective analysis was done in ten male patients with the disease, none of whom carried the R40H mutation and the other, the Y55D mutation in the OTC gene. A total of 32 factors were first compared in the two groups were further subjected to simple regression analysis, which revealed that age at onset, peak plasma ammonia concentration, concentrations in plasma of eight amino acids were determined to be significant predictors.
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[Publications] Nishiyori A, Yoshino M, Kato H, Matsuura T, Hoshide R, Matusda I, Kuno T, Miyazaki S, Hirose S, Kuromaru R, Mori M: "The R40H mutation in late onset type of human ornithine transcarbamylase deficiency in male patients"Hum Genet. 99. 171-176 (1997)
Description
「研究成果報告書概要(欧文)」より
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