| Project/Area Number |
12480227
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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 |
Nerve anatomy/Neuropathology
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| Research Institution | KYUSHU UNIVERSITY |
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Principal Investigator |
YOSHIDA Hiroki Med. Inst. Bioreg., Kyushu University, Ass. Prof., 生体防御医学研究所, 助教授 (40260715)
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| Co-Investigator(Kenkyū-buntansha) |
MOTOYAMA Noboru Nat. Inst. Longevity Sci., Dept. Geriat. Res., Kyushu University, Chief, 老年病研究部, 室長 (50277282)
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| Project Period (FY) |
2000 – 2001
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| Project Status |
Completed (Fiscal Year 2001)
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| Budget Amount *help |
¥13,500,000 (Direct Cost: ¥13,500,000)
Fiscal Year 2001: ¥4,600,000 (Direct Cost: ¥4,600,000)
Fiscal Year 2000: ¥8,900,000 (Direct Cost: ¥8,900,000)
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| Keywords | Apaf1 / neuron / apoptosis / mitochondria / Apafl / Bcl-xL |
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| Research Abstract |
The investigators have reported that Apaf1, an adaptor molecule that works for the mitochondrial pathways of apoptosis, is strongly expressed in the brain of embryos and also that Apaf1-deficient embryos showed brain deformities due to accumulation of neurons that failed to die by apoptosis. Contrary, mice that lack Bcl-xl, a regulatory molecule of the mitochondrial pathways of apoptosis, have been shown by the investigators to have excess of apoptotic neurons. The aim of the project is to analyze the regulatory mechanisms of apoptosis during the development of brains by generating mice that lack both Apaf1 and Bcl-xl (double KO mice).
The double KO embryos showed similar brain deformities to Apaf1-single mutant embryos. They also showed loss of apoptotic neurons, as did Apaf1-single mutant embryos. Thus, Bcl-xl-deficiency could not restore the phenotypes of Apaf1-deficiency. Interestingly, the double KO embryos died at the same time (around 13.5 days of embryogenesis) as Bcl-xl-single mutant embryos. Massive apoptosis of hematopoietic cells in fetal liver was observed in the double KO mice, as in Bcl-xl-single mutant embryos. It has been suggested that Apaf1 and Bcl-xl differentially regulate the apoptosis of neurons during embryogenesis.
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