| Project/Area Number |
61440093
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| Research Category |
Grant-in-Aid for General Scientific Research (A)
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| Allocation Type | Single-year Grants |
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| Research Field |
分子遺伝学・分子生理学
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| Research Institution | Institute for Protein Research,Osaka University. |
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Principal Investigator |
MIKOSHIBA Katsuhiko Professor Institute for Protein Research,Osaka University, 蛋白質研究所, 教授 (30051840)
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| Co-Investigator(Kenkyū-buntansha) |
NIINOBE Michio Research Assistant Institute for Protein Research,Osaka University, 蛋白質研究所, 助手 (80135748)
IKENAKA Kazuhiro Research Assistant Institute for Protein Research,Osaka University, 蛋白質研究所, 助手 (00144527)
OKANO Hideyuki Research Assistant Institute for Protein Research,Osaka University, 蛋白質研究所, 助手 (60160694)
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| Project Period (FY) |
1986 – 1988
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| Project Status |
Completed (Fiscal Year 1988)
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| Budget Amount *help |
¥24,700,000 (Direct Cost: ¥24,700,000)
Fiscal Year 1988: ¥5,000,000 (Direct Cost: ¥5,000,000)
Fiscal Year 1987: ¥6,000,000 (Direct Cost: ¥6,000,000)
Fiscal Year 1986: ¥13,700,000 (Direct Cost: ¥13,700,000)
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| Keywords | myelin basic protein (MBP) / myelin deficient(mld) / プロテオリピド蛋白質 / jimpy / mylin deficient(mld) / プロモーター活性 / 遺伝子再構成 / protelipid protein / jimpy mutant / myelin basic protein / myelin |
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| Research Abstract |
The myelin deficient (mld) is an autosomal recessive mutation in mice and is allelic to shiverer, a deletion mutation of the myelin basic protein (MBP) gene. MBP is expressed specifically in the oligodendrocyte and incorporated into the myelin sheath, by making myelin lamellae compact. MBP expression is considered to be completely absent in shiverer. In the present studies, it was demonstrated that MBP expression was greatly reduced in mld, but that it was still detectable. The level of protein as well as mRNA of MBP in mld was quantitated to be about 3% of that in the control on the myelinating stage. MBP mRNA in mld was initiated from the correct position, processed precisely and translated efficiently. Thus it was considered that reduced MBP expression in mld is mainly determined by the level of mRNA. The distribution of MBP expressed in mld was characterized immunohistochemically, and a mosaic expression of MBP was found in the myelin of the mld mice. The reason for heterogeniety in amount of MBP expression in each oligodendrocyte of mld observed here is still to be elucidated. Southern blot studies showed that entire region of the MBP gene is duplicated in mld. The respective 5'-flanking regions of the duplicated MBP genes (gene-1 and gene-2) of mld were isolated and characterized in their function and structure. The reduced mRNA level was not attributed to the defect of the promoter region, from the results of in vitro transcription and transient transcription assays. Finally we found that antisense RNA of MBP gene is trans-cribed due to the inversion and inhibits the expression of normal MBP mRNA in mld.
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