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1999 Fiscal Year Final Research Report Summary

Molecular Mechanism of Localization of the Mutant Ornithine Transcarbamylase to Mitochondrial Compartment

Research Project

Project/Area Number 09670854
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Pediatrics
Research InstitutionKURUME UNIVERSITY

Principal Investigator

YOSHINO Makoto  Kurume University, School of Medicine, Department of Pediatrics & Child Health, Professor, 医学部, 教授 (40080569)

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)
Project Period (FY) 1997 – 1999
Keywordsornithine transcarbamylase / mitochondria / localization
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.

  • Research Products

    (12 results)

All Other

All Publications (12 results)

  • [Publications] 芳野 信: "先天性高アンモニア血症の臨床と分子病理"久留米医学会雑誌. 60. 241-249 (1997)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 芳野 信: "高アンモニア血症"小児内科. 31. 605-608 (1999)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 原田直樹、芳野 信他: "先天代謝異常症の出生前診断とその問題点"周産期医学. 29. 1163-1167 (1999)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Nishiyori A, et al.: "The R40H mutation in a late onset type human ornithine transcarbamylase deficiency in male patients"Hum Genet,. 99. 171-176 (1997)

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      「研究成果報告書概要(和文)」より
  • [Publications] Nishiyori A, et al.: "Y55D mutation in ornithine transcarbamylase associated with late-onset hyperammonemia in a male"Hum Mutat. Suppl 1. S131-S133 (1998)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 芳野 信、西依 淳他: "男子遅発型ornithine transcarbamylase(OTC) 欠損症の臨床像と予後因子"日本先天代謝異常学会雑誌、in press.

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      「研究成果報告書概要(和文)」より
  • [Publications] Yoshino M: "Clinical aspects and molecular pathology of congenital hyperammonemia"J Kurume Med Assoc. 60(in Japanese). 241-249 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
  • [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
  • [Publications] Yoshino M, Nishiyori A, Koga Y, Mizushima Y, Maeshiro H, Inoue T, Izumi S, Hatase T, Yakushiji M, Kato H: "Potential pitfall prenatal enzymatic diagnosis of carbamoyl-phosphate synthetase I deficiency"J Inher Metab Dis. 20. 711-712 (1997)

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      「研究成果報告書概要(欧文)」より
  • [Publications] Nishiyori A, Yoshino M, Tananari Y, Hoshide R, Matsuda I, Mori M, Kato H: "Y55D mutation in ornithine transcarbamylase associated with-onset hyperammonemia in a male"Hum Mutat. Suppl 1. S131-S133 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Yoshino M: "Hyperammonemia"Shouni-Naika. 31(in Japanese. 605-608 (1999)

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  • [Publications] Harada N, Yoshino M, Tokunaga Y, Yoshida I, Inokuchi T, Murakami H, Aramaki S, Kuwano S, Koga Y, Akita Y: "Prenatal diagnosis for inborn errors of metabolism and pertinent issues"Shusanki Igaku (Prenatal Medicine). 29(in Japanese). 1163-1167 (1999)

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Published: 2001-10-23  

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