| Project/Area Number |
04044094
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| Research Category |
Grant-in-Aid for international Scientific Research
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| Allocation Type | Single-year Grants |
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| Section | Joint Research |
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| Research Institution | Kyoto University, Faculty of Medicine |
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Principal Investigator |
NAKANO Toru Kyoto University, Faculty of Medicine, Lectureer, 医学部, 講師 (00172370)
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| Co-Investigator(Kenkyū-buntansha) |
TSUBATA Takeshi Kyoto University, Faculty of Medicine, 医学部, 助教授 (80197756)
ASHBURNER Michael Cambridge University
MAK Tak W. Ontario Cancer Institute, Toronto University
清水 章 京都大学, 遺伝子実験施設, 教授 (00162694)
川市 正史 京都大学, 医学部, 助教授 (00195041)
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| Project Period (FY) |
1992 – 1993
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| Project Status |
Completed (Fiscal Year 1993)
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| Budget Amount *help |
¥8,000,000 (Direct Cost: ¥8,000,000)
Fiscal Year 1993: ¥3,900,000 (Direct Cost: ¥3,900,000)
Fiscal Year 1992: ¥4,100,000 (Direct Cost: ¥4,100,000)
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| Keywords | Gene targeting / Homologous recombination / Embryonic lethal / Development / Transcriptional regulator / 胚性幹細胞 / ショウジョウバエ / 末梢神経 / 遺伝子組換え |
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| Research Abstract |
The Jkappa-RBP gene was cloned as the gene which encodes the protein binding to the immunoglobulin recombination signal sequence flanking the kappa-type J segment (Jkappa-RS). However, expression of the gene is not restricted to the lymphoid system. And no functions of mouse Jkappa-RBP other than binding to Jkappa-RS have been found. Meanwhile, the Drosophila homologue of Jkappa-RBP gene turned out to be the gene known as Suppressor of Hairless (Sup(H)) whose mutation affects peripheral nervous system development, suggesting that the Jkappa-RBP gene is also involved in mouse neural development.
To elucidate the functions of Jkappa-RBP gene in mice, we have used homologous recombination in embryonic stem (ES) cells to derive null alleles of the gene. Mouse chimeras produced from two ES clones transmitted the mutated allele to their offspring. Mice with one disrupted Jkappa-RBP allele did not show any overt abnormalities. Heterozygotes for the mutation in the Jkappa-RBP gene were intercrossed to assess the effect of the loss of Jkappa-RBP in homozygous offspring. None of the new born and adult mice were homozygotes suggesting homozygous lethality at embryonic stage. Genotype analysis of embryos shows that homozygous embryos die between day 8.5 and 10.5 of gestation. Homozygous embryos of day 9.5 show 1) anterior opening of neural tube, 2) incomplete turning, and 3) microencephaly.
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