1989 Fiscal Year Final Research Report Summary
Analysis of gene function using transgenic mice harboring antisense DNA.
| Project/Area Number |
63490020
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| Research Category |
Grant-in-Aid for General Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Research Field |
広領域
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| Research Institution | School of Medicine, Tokai University |
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Principal Investigator |
KIMURA Minoru Tokai Univ. School of Med. Associate Prof., 医学部, 助教授 (10146706)
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| Co-Investigator(Kenkyū-buntansha) |
UEYAMA Yoshito Tokai Univ. School of Med. Associate Prof., 医学部, 助教授 (30072408)
YOKOYAMA Minesuke Central Institute for Experimental Animals Researcher, 研究員 (40090930)
KATSUKI Motoya Tokai Univ. School of Med. Prof., 医学部, 教授 (20051732)
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| Project Period (FY) |
1988 – 1989
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| Keywords | Transgenic mice / Antisense DNA / Genetic engineering / Embryo manipulation / Model for diseases / Myelin formation |
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| Research Abstract |
The aim of this project is to construct the transgenic mice which reduce the expression of the target gene using antisense DNA and to reveal the exact function of the individual gene in vivo based on the phenotype of these transgenic mice.
Recently, we have developed this system for the myelin basic protein (MBP) gene. In the transgenic mice which expressed antisense MBP RNA (minus-strand RNA complimentary to a MBP mRNA), the endogeneous MBP mRNA, the MBP and the myelination in the central nervous system were reduced and consequently shiverer phenotype appeared (Science 241, 593-595 (1988)). Further analysis revealed that the reduction of MBP mRNA and MBP occurred around two weeks after birth when MBP expression and myelin formation of normal mice become active. The reduction level was correlated with the extent of shivering phenotype. Moreover, all kinds of the antigenically-related MBPs were simultaneously reduced in the antisense MBP transgenics, although the antisense cDNA used corresponded to the single kind of several MBP mRNA produced by alternative splicing.
To apply this system for other genes, we have made the antisense cDNA constructs of three genes (beta-actin, c-Ha-ras and dystrophin genes) under the appropriate promoters and produced the transgenic mice. Total 31 transgenic lines were established but no prominent phenotype were recognized until now. The expression of the antisense transgene was very low in the several transgenic mice so far examined.
Together with extensive analyses of these transgenic mice, we are now improving the structure of the introduced DNA to increase the antisense RNA expression.
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[Publications] Katsuki,M.,Sato,M.,Kimura,M.,Yokoyama,M.,Kobayashi,K.& Nomura,T.: "Conversion of Normal Behavior to Shiverer by Myelin Basic Protein Antisense cDNA in Transgenic Mice." Science. 241. 593-595 (1988)
Description
「研究成果報告書概要(和文)」より
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[Publications] Kimura,M.,Sato,M.,Akatsuka,A.,Nozawa-Kimura,S.,Takahashi,R.,Yokoyama,M.,Nomura,T & katsuki,M.: "Restoration of myelin formation by a single type of myelin basic protein in transgenic shiverer mice." Proc.Natl.Acad.Sci.USA. 86. 5661-5665 (1989)
Description
「研究成果報告書概要(和文)」より
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[Publications] Katsuki, M., Sato, M., Kimura, M., Yokoyama, M., Kobayashi, K. and Nomura, T.: "Conversion of Normal Behavior to Shiverer by Myelin Basic Protein Antisense cDNA in Transgenic Mice." Science 241, 593-595 (1988).
Description
「研究成果報告書概要(欧文)」より
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[Publications] Kimura, M., Sato, M., Akatsuka, A., Nozawa-Kimura, S., Takahashi, R., Yokoyama, M., Nomura, T. and Katsuki, M.: "Restoration of myelin formation by a single type of myelin basic protein in transgenic shiverer mice." Proc. Natl. Acad. Sci. USA 86, 5661-5665 (1989).
Description
「研究成果報告書概要(欧文)」より
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