| Project/Area Number |
07457040
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Pathological medical chemistry
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| Research Institution | Osaka University |
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Principal Investigator |
SHIMADA Kazunori Professor Research Institute for Microbial Diseases, Osaka University, 微生物病研究所, 教授 (40037354)
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| Co-Investigator(Kenkyū-buntansha) |
SHIRAI Manabu Research Associate, Research Institute for Microbial Diseases, 微生物病研究所, 助手 (70294121)
TOMOTSUNE Daihachiro Research Associate, Research Institute for Microbial Diseases, 微生物病研究所, 助手 (80283802)
NOMURA Midori Research Associate, Research Institute for Microbial Diseases, 微生物病研究所, 助手 (60263315)
TAKIHARA Yoshihiro Associate Professor, Research Institute for Microbial Diseases, 微生物病研究所, 助教授 (60226967)
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| Project Period (FY) |
1995 – 1997
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| Project Status |
Completed (Fiscal Year 1997)
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| Budget Amount *help |
¥7,600,000 (Direct Cost: ¥7,600,000)
Fiscal Year 1997: ¥1,200,000 (Direct Cost: ¥1,200,000)
Fiscal Year 1996: ¥1,300,000 (Direct Cost: ¥1,300,000)
Fiscal Year 1995: ¥5,100,000 (Direct Cost: ¥5,100,000)
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| Keywords | bmil / polyomeotic / protein interactions / rae28 / Polycomb group / Hox / segment specification / neural crest / rae28遺伝子 / ショウジョウバエ / ポリホメオティック遺伝子 / 臓器形成不全 / ファロ-の四徴 / CATCH22症候群 / 神経堤細胞 |
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| Research Abstract |
1) A replacement vector convenient for introducing subtle mutations into various mouse genes has been developed using as a model system, the mouse transthyretin-encoding gene (ttr) and mouse embryonal carcinoma F9 cells. The vector consists of part of ttr carrying a subtle mutation in its second exon, and a cassette of the neomycin-resistance (neo) - and herpes simplex virus thymidine kinase (HSV-tk) -encoding genes flanked with a 3-kb duplication of mostly the second intron of ttr.
2) To study gene expression in undifferentiated mouse embryonal carcinoma F9 cell, we prepraed 2,132 expressed sequence tags (ESTs) and found that 1,416 match known gene and/or protein sequences. We tried to develop a system for characterizing ESTs matching no known genes. We also isolated 17 cDNA clones corresponding to mRNAs induced rapidly during retinoic acid-mediated F9 cell differentiation and characterized two of them, named rael and rae28, in this study.
3) To study the role of the rae28gene in mouse development, we generated rae28-deficient mice by gene targeting in embryonic stem cells. To our surprise, the homozygous rae28-knock out mice carried all the phenotypes noted in the human congenital disorder CATCH-22 syndrome. We found that the anterior boundaries of Hoxa-3, a-4, a-5, b-3, b-4 and d-4 expression are shifted in the rostral direction in the paraxial mesoderms of the rae28-/- homozygous embryos, and those of Hoxb-3 and b-4 expression are also similarly altered in the rhombomeres and/or pharyngeal arches. These altered Hox codes were presumed to be correlated with the posterior skeletal transformations and neural crest defects observed in the rae28-/- homozygous mice. These results indicate that the rae28 gene is involved in the regulation of Hox gene expression and segment specification during paraxial mesoderm and neural crest development.
4) We continued studies on mouse models for familial amyloidotic polyneuropathy.
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