| Project/Area Number |
25461631
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Pediatrics
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| Research Institution | Keio University |
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Principal Investigator |
Maeda Jun 慶應義塾大学, 医学部, 助教 (00255506)
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| Co-Investigator(Kenkyū-buntansha) |
TSUCHIHASHI TAKATOSHI 慶應義塾大学, 医学部, 共同研究員 (10286528)
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| Co-Investigator(Renkei-kenkyūsha) |
YAMAGISHI HIROYUKI 慶應義塾大学, 医学部, 准教授 (40255500)
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| Project Period (FY) |
2013-04-01 – 2016-03-31
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| Project Status |
Completed (Fiscal Year 2015)
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| Budget Amount *help |
¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000)
Fiscal Year 2015: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2014: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2013: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
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| Keywords | 心臓流出路 / 先天性心疾患 / 遺伝子 / 環境因子 / 心臓流出路発生 / Tbx1遺伝子 / 葉酸 / Ｔｂｘ１遺伝子 / 大動脈弓発生 / レチノイン酸 |
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| Outline of Final Research Achievements |
Tbx1 is an essential transcription factor required for development of the cardiac outflow tract and artic arch. Our genetically engineered Tbx1 hypomorphic (Tbx1neo/neo) mice display a severe congenital heart defect, persistent truncus arteriosus (PTA), reminiscent of 22q11.2 deletion syndrome in human. We compared cardiovascular phenotype of Tbx1neo/neo embryos from pregnant mice fed with usual diet (CO) and with folic acid rich diet (FA). All of CO embryos showed severe form of PTA, meanwhile 25 percent of FA embryos showed milder form of PTA. The number of migrated neural crest cells were reduced in developing cardiac outflow tract of CO embryos compared with wild type, whereas the migration of neural crest cells was restored in FA embryos. These results suggest that PTA in Tbx1neo/neo embryos results from genetic background can be modified by nutrition and the environmental adjustment during pregnancy may rescue the cardiovascular phenotype.
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