2004 Fiscal Year Final Research Report Summary
The function of the EAT, an inhibitor of apotptosis, in vivo and its molecular mechanism in disease
| Project/Area Number |
13470053
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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 |
Experimental pathology
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| Research Institution | National Research Institute for Child Health and Development (2002-2004)
Keio University (2001) |
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Principal Investigator |
UMEZAWA Akihiro National Research Institute for Child Health and Development, Department for Reproductive Biology and Pathology, Director, 部長 (70213486)
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| Co-Investigator(Kenkyū-buntansha) |
HATA Junichi National Research Institute for Child Health and Development, Chairman, 所長 (90051614)
OKITA Hajime National Research Institute for Child Health and Development, Department of Developmental Biology, Chief, 発生・分化研究部, 室長 (50317260)
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| Project Period (FY) |
2001 – 2004
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| Keywords | Apoptosis / Development / EAT Gene / ES Cells / Conditional Targetting / Bcl-2 Family / Transgenic Mouse |
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| Research Abstract |
EAT/mcl1 gene was isolated as a gene which was up-regulated at the early stage of differentiation of human embryonal carcinoma cells and belonged to the bcl-2 related gene. We have previously shown that it confered resistance to apoptosis induced by chemotherapeutic agents in cultured fibroblasts and mice overexpressing this gene exhibited hyperplasia of pancreatic islet. In order to clarify the function of the EAT/mcl-1 in vivo, we have disrupted the EAT/mcl1 gene in embryonic stem cells and generated knock out mice.
We have established 11 embryonic stem cell lines in which one allele of the EAT/mcl1 exon 1 was flanked by loxP sequence and a selection casette. Three lines of mice were generated by injecting the targeted cells into murine early embryos. Crossing with Cre expressing transgenic mice, we have generated heterozygous EAT null mice and floxed mice. This heterozygous mice(EAT-/+) was morphologically indistinguishable with wild type animals. This indicates the half dose of EAT/mcl-1 is sufficient to normal development. Crossing the floxed mice with tissue specific cre expressing mice, we can nullify the EAT gene in conditional manner. We have introduced mox2 cre transgenic mice which express cre in epiblast derived embryonic tissues to knock out the EAT gene.
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