| Project/Area Number |
09680792
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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 Institution of Physical and Chemical Research (RIKEN) (1998)
Kyoto University (1997) |
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Principal Investigator |
IKEDA Toshio Riken, Behavioral Genetics, Scientist, 行動遺伝学技術開発チーム, 研究員 (80252526)
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| Co-Investigator(Kenkyū-buntansha) |
ITOHARA Shigeyoshi Behavioral Genetics, Team Leader, 行動遺伝学技術開発チーム, チームリーダー(研究職) (60252524)
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| Project Period (FY) |
1997 – 1998
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| Project Status |
Completed (Fiscal Year 1998)
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| Budget Amount *help |
¥3,200,000 (Direct Cost: ¥3,200,000)
Fiscal Year 1998: ¥1,400,000 (Direct Cost: ¥1,400,000)
Fiscal Year 1997: ¥1,800,000 (Direct Cost: ¥1,800,000)
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| Keywords | transcription factor / embryonic lethal / homologous recombination / knockout mouse / transgenic mouse / Otf6 / 細胞周期 / コンディショナルノックアウトマウス |
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| Research Abstract |
Mouse lacking the entire Otf6 (Oct-6, Scip, Tst-1) gene locus was generated by homologous recombination in embryonic stem cells. The heterozygous mutants developed normally and were fertile. No homozygous mutant offspring were obtained from intercrosses of heterozygotes, suggesting that this deletion mutation of Otf6 locus was essential for embryonic development. Homozygous mutant embryos died before 8 days post-coitus (dpc). The homozygous mutants were characterized by small size and morphological abnormality compared to the heterozygous mutants and wild types at 7.5 dpc. In addition the BrdU incorporation rate of embryo was reduced in homozygous mutants. In situ labeling for the fragmentation of the genome (TUNEL) suggested that apoptosis occurs in the embryonic cells of homozygous mutant. Consistent with the in vivo results, homozygous mutant manifested growth arrest and rapid death of the inner cell mass in vitro. It has been shown that Mdm2 and Brca1 deficient embryos arrested growth and died at similar embryonic stages. We found that expression of m dm2 but not Brca1 was nearly abolished in homozygous mutant embryos. These results suggest that the developmental arrest of the Otf6 deletion mutants could be caused by the m dm2 pathway.
To analyze the function of Otf6 in adult mouse brain, we produced the conditional gene targeting system using Cre-loxP system and are confirming the specificity of Cre recombinase expression in brain.
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