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1997 Fiscal Year Final Research Report Summary

Positional cloning of carnitine trasporter gene and its comtribution to the pathophysiological changes

Research Project

Project/Area Number 08457267
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field 内分泌・代謝学
Research InstitutionThe University of Tokushima

Principal Investigator

KUWAJIMA Masamichi  School of Medicine, The University of Tokushima Assoc.Prof., 医学部, 助教授 (00205262)

Co-Investigator(Kenkyū-buntansha) TOKINO Takashi  University of Tokyo, Institute of Medical Science, Assoc.Prof., 医科学研究所, 助教授 (40202197)
MURAKAMI Takashi  School of Medicine, The University of Tokushima Instructor, 医学部, 助手 (40210009)
NOMA Yoshihiko  Medical School Hospital, The University of Tokushima Assis.Prof., 医学部・附属病院, 講師 (10218349)
Project Period (FY) 1996 – 1997
KeywordsCarnitine / Carnitine Transporter / fatty liver / primary carnitine deficiency / hypoglycemia / cardiomegaly / mitochondria / hyperammonemia
Research Abstract

The exact roles playd by carnitine in vivo have remained unclear. Our recent discovery of mice with systemic carnitine dificiency (JVS mice) offers the possibility of improvement of this circumstance. These JVS mice show symptoms such as fatty liver, hyperammonemia, hypoglycemia, cardiomegaly and skeletal muscle degeneration. We have been analyzin the histological, biochemical and molecular biological features of tissues from various sites of their bodies, focusing on the analysis of the relationship between carnitine deficiency and the diverse symptoms exhibited by these mice.
We have obtained the following findings :
1. As early as 2 weeks of age, JVS mice had higher absolute heart weights and higher retios of heart weight to body weight than controle mice. Hypertrophy of my ocardial cells was seen, and the nuclei of these cells tended to be larger in JVS mice. When observed under an electron microscope, the nuclei were slightly hypertrophic and not a few cells showed marked increase in mitochondria. The levels of carnitine palmitoyl transferase I (CPTI) mRNA and CPT II mRNA differted from those in controle mice.
2. High-affinity carnitine transport activity was absent in the fibroblasts of JVS mice. This indicates that JVS mice can serve as an animal model of human primary carnitine dificiency.
3. The symptoms seen in JVS mice are genetically transmitted in an autosomal recessive manner. It is thougt that a single gene is responsible for all these symptoms. The JVS gene was located on chromosome 11.

  • Research Products

    (12 results)

All Other

All Publications (12 results)

  • [Publications] Hotta, K.: "Altered expresion of carnitine palmitoyltransferase II in liver,muscle,and heart of mouse strain with juvenile visceral steatosis" Biochim.Biophys.Acta. 1287. 131-135 (1996)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Uenaka, R.: "Increased expression of carnitine palimitoyltransferase I gene is repressed by administering L-carnitine in the hearts of carnitine dificient juvenile visceral steatosis mice" J,Biochem.119. 533-540 (1776)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Okita, K.: "Definition of the locus responsible for systemic carnitine deficiency within a 1.6-cm region of mouse chromosome-II by detailed linkage analysis" Genomics. 33. 287-291 (1996)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Kuwajima, M.: "Carnitine transport defect in fibroblasts of juvenile visceral steatosis(JVS) mouse" Biochem.Biophys.Res.commun.223. 283-287 (1996)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Narama, I.: "Heterogeneity of histopathologic featurea in the congenitally carnitine deficient juvenile visceral steatosis(JVS)mouse" Biomed.Res.18. 247-255 (1977)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Kaido, .M.: "Mitochondrial abnormalities in a marine model of primary carnitine deficiency systemic pathology and trial of replacement therapy" Eur.Neurology. 38. 302-309 (1997)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] K.Hotta, M.Kuwajima, A.Ono, R.Uenaka, H.Nakajima, J.Miyagawa, M.Namba, T.Hanafusa, M.Horiuchi, H.Nikaido, J.Hayakawa, N.Kono, T.Saheki, Y.Matsuzawa: "Altered Expression of Carnitine Palmitoyltransferase II in Liver, Muscle and Heart of Mouse Strain with Juvenile Visceral Steatosis." Biochim.Biophys.Acta. 1289. 131-135 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] R.Uenaka, M.Kuwajima, A.Ono, Y.Matsuzawa, J.Hayakawa, N.Inohara, Y.Kagawa, S.Ohta: "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 (3). 533-540 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] K.Okita, T.Tokino, H.Nishimori, K.Mimura, H.Nikaido, J.Hayakawa, A.Ono, M.Kuwajima, Y.Matsuzawa, and Y.Nakamura: "Definition of the Locus Reponsible for Systemic carnitine Deficiency within a 1.6cM Region of Mouse Chromosome 11 by Detailed Linkage Analysis." Genomic. 33. 289-291 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] M.Kuwajima, K.Lu, A.Harashima, A.Ono, I.Sato, A.Mizuno, T.Murakami, H.Nakajima, J.Miyagawa, M.Namba, T.Hanafusa, J.Hayakawa, Y.Matsuzawa, and K.Shima: "Carnitine Transport 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
  • [Publications] I.Narama, K.Ozaki, T.Matsuura, A.Ono, M.Sei, K.Shima, M.Kuwajima: "Heterogeneity of histopathologic features in the congenitally carnitine-deficient juvenile visceral steatosis (JVS) mouse." Biomed.Res.18 (3). 247-255 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] M.Kaido, H.Fujimura, A.Ono, K.Toyooka, H.Yoshikawa, T.Nishimura, K.Ozaki, I.Narama and M.Kuwajima: "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

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Published: 1999-03-16  

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