1997 Fiscal Year Final Research Report Summary
Evaluation of disease model traits in cultured cells derived from carnitine deficient JVS mice
| Project/Area Number |
08458274
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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 |
Laboratory animal science
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| Research Institution | Kanazawa University |
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Principal Investigator |
HAYAKAWA Jun-ichiro Kanazawa Univ., Faculty of Medicine, Professor, 医学部, 教授 (50110622)
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| 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)
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| Project Period (FY) |
1996 – 1997
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| Keywords | mice / animal model / fatty liver / sperm / cardiac hypertrophy / transporter / carnitine / cultured cells |
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| 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.
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