PRODUCTION OF MYOPHATIC MODEL MICE WITH GENETIC CAVEOLIN-3 DEFICIENCY AND PHATHOLOGICAL ANALYSIS OF THEIR MUSCLES
| Project/Area Number |
10670224
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Experimental pathology
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| Research Institution | NATIONAL INSTITUTE OF NEUROSCIENCE NCNP |
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Principal Investigator |
HAGIWARA Yasuko NATIONAL INSTITUTE OF NEUROSCIENCE, NCNP, SECTION CHIEF, 神経研究所, 室長 (00175530)
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| Project Period (FY) |
1998 – 2000
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| Project Status |
Completed (Fiscal Year 2000)
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| Budget Amount *help |
¥3,300,000 (Direct Cost: ¥3,300,000)
Fiscal Year 2000: ¥800,000 (Direct Cost: ¥800,000)
Fiscal Year 1999: ¥900,000 (Direct Cost: ¥900,000)
Fiscal Year 1998: ¥1,600,000 (Direct Cost: ¥1,600,000)
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| Keywords | CAVEOLIN-3 / GENE KNOCK-OUT MICE / MUSCULAR DYSTROPHY / SKELETAL MUSCLE / カベオリン-1 / 心筋 / 平滑筋 |
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| Research Abstract |
Caveolin-3 is a muscle-specific protein integrated in the caveolae, which are small invaginations of the plasma membrane. Mutations of the caveolin-3 gene, localized at 3p25, have been reported to be involved in the pathogenesis of limb-girdle muscular dystrophy(LGMDIC or caveolinopathy) with mild clinical symptoms, inherited through autosomal dominant form of genetic transmission. To elucidate the pathogetic mechanism, we developed caveolin-3-deficient mice for use as animal models of caveolinopathy. Caveolin-3 mRNA and its protein were absent in homozygous mutant mice. In heterozygous mutant mice, both the mRNA and its protein were normal in size, but their amounts reduced by about half. The density of caveolae in skeletal muscle plasma membrane was roughly proportional to the amount of caveolin-3. In homozygous mutant mice, muscle degeneration was recognized in soleus muscles at 8 weeks of age and in the diaphragm from 8 weeks to 30 weeks, although there was no difference in growth and movement between wild-type and mutant mice. No apparent muscle degeneration was observed in heterozygous mutant mice, indicating that pathological changes caused by caveolin-3 gene disruption were inherited through the recessive form of genetic transmission.
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Report
(4 results)
Research Products
(13 results)
