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Evaluation of disease model traits in cultured cells derived from carnitine deficient JVS mice

Research Project

Project/Area Number 08458274
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Laboratory animal science
Research InstitutionKanazawa University

Principal Investigator

HAYAKAWA Jun-ichiro  Kanazawa Univ., Faculty of Medicine, Professor, 医学部, 教授 (50110622)

Co-Investigator(Kenkyū-buntansha) KUWAJIMA Masamichi  Tokushima Univ., School of Medicine, Assoc.Professor, 医学部, 助教授 (00205262)
HASHIMOTO Noriyoshi  Kanazawa Univ., Faculty of Medicine, Instructor, 医学部, 助手 (50242524)
TAMAI Ikumi  Kanazawa Univ., Faculty of Pharm., Assoc.Professor, 薬学部, 助教授 (20155237)
Project Period (FY) 1996 – 1997
Project Status Completed (Fiscal Year 1997)
Budget Amount *help
¥5,200,000 (Direct Cost: ¥5,200,000)
Fiscal Year 1997: ¥1,800,000 (Direct Cost: ¥1,800,000)
Fiscal Year 1996: ¥3,400,000 (Direct Cost: ¥3,400,000)
Keywordsmice / animal model / fatty liver / sperm / cardiac hypertrophy / transporter / carnitine / cultured cells / 遺伝子量
Research Abstract

JVS mice which are homozygous for recessive mutant gene jvs exhibit various pathological syndromes, such as fatty liver, htperanmonemia, cardiac hypertrophy, reduced fertility in males, and abnormal ; expression of genes related to urea cycle enzymes. In this project we attempt to assess the basis of these syndromes in primary cultured cells or establisjed cell lined from the JVS embryos.
Although we have newly made following findings, it is concluded that various specific syndromes in the JVS mice are difficult to predict from cultured cells from the JVS embryos or new born pups. It seems that further elaborated methods for cell or tissue culture are neede to assess the syndrome in vivo.
1. In enlarged heart muscle some muscle cells have an enlarged nucleus and the increased mitochondoria.
2. As seen in sliced kidney, primary cultured embryonic cells and established fibloblastic cells are less active in uptake of free carnitine. The carnitine uptake in in vitro is depend on gene dose of mutant gene jvs.
3. Although spermatogenesis in JVS is apparently morphologically normal, it seems that the maturation process in epydidimus is impaired, and it resulted in partial sterility in JVS male mice.
4. Cold-Induced thermogenesis in JVS was blunted even in the most general condition of laboratory animal room and that the blunted thermogenesis was partially improved with L-carnitine supplement.
5. Volume distribution of free carnitine after ^3H-labeled carnitine administration (oral or iv) was significantly reduced and the concentration of free carnitin various organs except brain relative to that of plasma is also lower compared normal controls and bioavailability of free carnitine after oral administration of carnitine in JVS was about 50% of normal control value.

Report

(3 results)
  • 1997 Annual Research Report   Final Research Report Summary
  • 1996 Annual Research Report
  • Research Products

    (27 results)

All Other

All Publications (27 results)

  • [Publications] N.Hashimoto: "Gene-dose effect on carnitine transport activity in embryonic fibroblasts of JVS mice as a model of human carnitine transporter deficiency" Biochem.Pharmacol.55(in press). (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] I.Narama: "Heterogeneity of histopathologic features in thecongenitally carnitine-deficient juvenile visceral steatosis(JVS)mouse." Biomed.Res. 18. 247-255 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] M.Kaido: "Mitochondrial abnormalities in a murine model of primary carnitine deficiency." European Neurology. 38. 302-309 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] M.Kuwajima: "Characteristics of cardiac hypertrophy in the juvenile visceral steatosis mouse with systemic carnitine deficiency." J.Mol.Cell.Cardiol.(in press).

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] M.Kuwajima: "Carnitine transport defect in fibroblast of juvenile visceral steatosis(JVS)mice." Biochem.Biophys.Res.Commun.223. 233-287 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] K.Okita: "Definition of the locus resopnsible for systemic carnitine deficiency with in a 1.6cM region of a 1.6cM region of mouse chromosome 11 by detailed linkage analysis." Genomics. 33. 289-291 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] R.Uenaka: "Increased expression of carnitine palmitoyltransferase I gene is repressed by administration of carnitine in the heart of carnitine deficient juvenile visceral steatosis mice" J.Biochem.119. 533-540 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] K.Hotta: "Altered expression of carnitine palmitoyItransferase II in liver,muscle and heart of mouse strain with juvenile visceral steatosis." Biochem.Biophys.Acta. 1289:. 131-134 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] K.Hotta: "Disordered expression of glycolytic and gluconeogenic liver enzymes of juvenile visceral steatosis mice with systemic carnitine deficiency." Diabetes Res.Clin.Pract.32. 117-123 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] M.Kuwajima, et al.: "Characteristics of cardiac hypertrophy in the juvenile visceral steatosis mouse with systemic carnitine deficiency" J.Mol.Cell.Cardiol.(in press).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] N.Hashimoto, et al.: "Gene-dose effect on carnitine transport activity in embryonic fibroblasts of JVS mice as a model of human carnitine transporter deficiency." Biochemical Pharmacology. 55. xxx-xxx (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] I.Narama, et al.: "Heterogeneity of histopathologic features in the congenitally carnitine-deficient juvenile visceral steatosis (JVS) mouse." Biomed.Res.18. 247-255 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] M.Kaido, et al.: "Mitochondrial abnormalities in a murine model of primary carnitine deficiency." European Neurology. 38 (4). 302-309 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] M.Kuwajima, et al.: "Carnitine transporter defect in fibroblast of Juvenile visceral steatosis (JVS) mouse. Biochem." Biophys.Res.Commun.223. 283-287 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] K.Okita, et al.: "Definition of the locus responsible for systemic carnitine deficiency within a 1.6 cM region of mouse chromosome 11 by detailed linkage analysis." Genomics. 33. 289-291 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] K.Hotta, et al.: "Desordered expression of glycolytic and gluconeogenic liver enzymes of juvenile visceral steatosis mice with systemic carnitine deficiency." Diabetes Res.Clin.Pract.32. 117-123 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] R.Uenaka, et al.: "Increased expression of carnitine palmitoyltransferase I gene is repressed by administration of carnitine in the heart of carnitine deficient juvenile visceral steatosis mice." J.Biochem.119. 533-540 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] K.Hotta, et al.: "Altered expression of carnitine palmitoyltransferase II in liver, muscle and heart of mouse strain with juvenile visceral steatosis. Biochem." Biophys.Acta. 1289. 131-134 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] N.Hashimoto: "Gene-dose effect on carnitine transport activity in embryonic fibroblasts of JVS mice as a model of human carnitine transporter deficiency" Biochem.Pharmacol.55(in press). (1998)

    • Related Report
      1997 Annual Research Report
  • [Publications] I.Narama: "Heterogeneity of histopathologic features in thecongenitally carnitine-deficient juvenile visceral steatosis(JVS)mouse." Biomed.Res. 18. 247-255 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] M.Kaido: "Mitochondrial abnormalities in a murine model of primary carnitine deficiency." European Neurology. 38. 302-309 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] M.Kuwajima: "Characteristics of cardiac hypertrophy in the juvenile visceral steatosis mouse with systemic carnitine deficiency." J.Mol.Cell.Cardiol.(in press).

    • Related Report
      1997 Annual Research Report
  • [Publications] K.Hotta: "Altered expression of carnitine palmitoyltransferase II in liver,muscle and heart of mouse strain with juvenile visceral steatosis" Biochem.Biophys.Acta. 1289. 131-135 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] R.Uenaka: "Increased expression of carnitine palmitoyltransferase I gene is repressed by administration of carnitine in the heart of carnitine deficent juvenile visceral steatosis mice." J.Biochemistry. 119. 533-540 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] K.Hotta: "Disordered expression of glycolytic and gluconeogenic liver enzymes of juvenile visceral steatosis mice with systemic carnitine deficiency." Diabetes Res.Clin.Pract.32. 117-123 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] K.Okita: "Definition of the locus responsible for systemic carnitine deficiency within a 1.6cM region of mouse chromosome 11 by detailed linkage analysis." Genomics. 33. 289-291 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] M.Kuwajima: "Carnitine transport defect in fibroblast of juvenile visceral steatosis(JVS) mouse." Biochem.Biphys.Res.Commun.223. 233-287 (1996)

    • Related Report
      1996 Annual Research Report

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Published: 1996-04-01   Modified: 2016-04-21  

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