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KAKEN_25461631seika.pdf
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Title |
Title |
心臓流出路および大動脈弓発生異常に関与する遺伝子と環境因子の影響
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Kana |
シンゾウ リュウシュツロ オヨビ ダイドウミャクキュウ ハッセイ イジョウ ニ カンヨスル イデンシ ト カンキョウ インシ ノ エイキョウ
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Shinzo ryushutsuro oyobi daidomyakukyu hassei ijo ni kanyosuru idenshi to kankyo inshi no eikyo
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The genetic and environmental effect on defects of developing cardiac outflow tract and aortic arch
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前田, 潤
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マエダ, ジュン
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Maeda, Jun
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慶應義塾大学・医学部・助教
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Research team head
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科研費研究者番号 : 00255506
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土橋, 隆俊
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ツチハシ, タカトシ
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Tsuchihashi, Takatoshi
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慶應義塾大学・医学部・共同研究員
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Research team member
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科研費研究者番号 : 10286528
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山岸, 敬幸
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ヤマギシ, ヒロユキ
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Yamagishi, Hiroyuki
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慶應義塾大学・医学部・准教授
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Research team member
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科研費研究者番号 : 40255500
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2016
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科学研究費補助金研究成果報告書
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2015
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Abstract |
心臓流出路発生に必須の転写因子Tbx1の発現を低下させたTbx1neo/neoマウスは, ヒト22q11.2欠失症候群同様, 総動脈幹症(PTA)を呈する。Tbx1neo/neo胎仔を妊娠した母マウスに, 栄養素である葉酸を通常量投与した(CO)群と多量投与した(FA)群で, 胎仔の心表現型を比較したところ, CO胎仔は全例重症型PTAを呈したが, FA胎仔では軽症型が25%認められた。心臓流出路に遊走する神経堤細胞数は, CO胎仔では減少していたが, FA胎仔ではその減少の程度が軽度だった。このモデルマウスによる検討から, 遺伝的要因で発症するPTAの重症度が, 環境的要因により軽症化する可能性が示唆された。
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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研究種目 : 基盤研究(C)(一般)
研究期間 : 2013~2015
課題番号 : 25461631
研究分野 : 小児循環器学
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