| Project/Area Number |
08457267
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
内分泌・代謝学
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| Research Institution | The University of Tokushima |
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Principal Investigator |
KUWAJIMA Masamichi School of Medicine, The University of Tokushima Assoc.Prof., 医学部, 助教授 (00205262)
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| 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)
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| Project Period (FY) |
1996 – 1997
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| Project Status |
Completed (Fiscal Year 1997)
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| Budget Amount *help |
¥4,700,000 (Direct Cost: ¥4,700,000)
Fiscal Year 1997: ¥2,400,000 (Direct Cost: ¥2,400,000)
Fiscal Year 1996: ¥2,300,000 (Direct Cost: ¥2,300,000)
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| Keywords | Carnitine / Carnitine Transporter / fatty liver / primary carnitine deficiency / hypoglycemia / cardiomegaly / mitochondria / hyperammonemia / カルニチン輸送担体 |
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| 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.
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