| Project/Area Number |
16591026
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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 |
Pediatrics
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| Research Institution | Osaka University |
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Principal Investigator |
SAKAI Norio Osaka University, Graduate School of Medicine, Assistant Professor, 医学系研究科, 講師 (30314313)
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| Co-Investigator(Kenkyū-buntansha) |
OKINAGA Takeshi Osaka University, Gaduate School of Medicine, Assistant, 医学系研究科, 助手 (30362734)
TANIIKE Masako Osaka University, Gaduate School of Medicine, Associate Professor, 医学系研究科, 助教授 (30263289)
OZONO Keiichi Osaka University, Graduate School of Medicine, Professor, 医学系研究科, 教授 (20270770)
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| Project Period (FY) |
2004 – 2005
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| Project Status |
Completed (Fiscal Year 2005)
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| Budget Amount *help |
¥3,400,000 (Direct Cost: ¥3,400,000)
Fiscal Year 2005: ¥1,300,000 (Direct Cost: ¥1,300,000)
Fiscal Year 2004: ¥2,100,000 (Direct Cost: ¥2,100,000)
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| Keywords | spina bifida / Lrp6 / Wnt signaling / pQCT / 葉酸 / 催奇性薬剤 / スクリーニング |
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| Research Abstract |
1)Selection of highly susceptible model mice for spina bifida : We prepare KO mice of Wnt receptor Lrp6 and KO mice of Pax1 after cleaning for SPF room. We observed the ratio of embryo having spina bifida produced with mating of Lrp6 heterozygous pair. We found this ratio was as high as 40% of all embryo produced with this mating.
2)Medicine treatment of pregnant mice ; We prepare mating of heterozygous mouse for each mutant and wild mouse. We treated the carbamazepine or valproic acid with several dose and different schedule. We produced the embryo at E12 and observed the ratio of embryos showing spina bifida.
3)Phenotypic analysis of embryo : We also produced homozygous embryo of rs (hypomorphic mutation of Lrp6) with heterozygous mating. The embryos were stained with Alcianblue and Alizarin for analyzing the abnormality of cartilage or bone formation. We found the abnormality of bone formation in rs/rs embryo. We analysed the bone measurement using pQCT method for bone density. In this observation we found loss of bone density at cancellous tissue in the tibia of rs/rs mouse for young and old mouse. We analysed the expression of Rankl gene in the osteoblast cells produced from rs/rs was increased.
4)Analysis of protective effect of folic acid aginst spina bifida ; We treated pregnant mice produced from rs heterozygous mating with folic acid for three days. We checked the ratio of spina bifida in the embryo of wild type and heterozygous type. We could not detect clear difference in this observation.
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