1996 Fiscal Year Final Research Report Summary
Generation and analysis of mGluR gene knockout mice
| Project/Area Number |
07680875
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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 |
Neuroscience in general
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| Research Institution | The University of Tokyo (1996)
Kyushu University (1995) |
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Principal Investigator |
ATSU Aiba The University of Tokyo, The Institute of Medical Science, Associate Professor, 医科学研究所, 助教授 (20271116)
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| Co-Investigator(Kenkyū-buntansha) |
NAKAMURA Kenji The University of Tokyo, The Institute of Medical Science, Research Associate, 医科学研究所, 助手 (90253533)
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| Project Period (FY) |
1995 – 1996
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| Keywords | metabotropic glutamate receptor / phospholipase C / G protein / norp A / Gllalpha / transgenic mice / ataxia / Purkinje cell |
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| Research Abstract |
To investigate the role of metabotropic glutamate receptors, mGluR1 and mGluR5 which are coupled to inositol phosphate/Ca^<2+> signal transduction and respond to quisqualate strongly, in the central nervous system, we planned to generate and analyze knockout mice which lack Gllalpha gene or phospholipase C-beta4 (PLC-beta4) gene. PLC-beta4 gene is strongly expressed in the retina and cerebellum. In 1996, targeting vector in which the part of PLC-beta4 gene was replaced by neo-gpt gene cassette, was introduced into embryonic stem cells by electropration. Homologous recombinants were injected into C57BL/6 blastocysts to generate chimeric mice. We are crossing chimeras with C57BL/6 mice to generate heterozygous mutant mice. Since PLC-beta4 is downstream of mGluR1 in Purkinje cells in cerebellum, it is interesting to compare the phenotype of mGluR1 knockout mice and that of PLC-beta4. Also we plan to generate double mutant mice which lack both of genes. On the other hand, we found that transgenic mice which express the constitutively active Gllalpha gene in the Purkinje cells, are ataxic. The cerebellum of these mice are smaller than that of wild type mice and lack Purkinje cells. This result indicates that the excessive stimulation of PLC-beta results in the degeneration of Purkinje cells and abnormal development of the cerebellum. To examine the relationship between the transgene expression and the development of Purkinje cells, we are carrying out in situ hybridization for mRNA of the transgene.
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