Analysis of the medaka intestinal atresia mutant

2018 Fiscal Year Final Research Report

• Project/Area Number: 15K08139
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: General anatomy (including histology/embryology)
• Research Institution: Kyoto Prefectural University of Medicine
• Principal Investigator: Kobayashi Daisuke 京都府立医科大学, 医学(系)研究科(研究院), 講師 (60376548)
• Project Period (FY): 2015-04-01 – 2019-03-31
• Keywords: 腸管閉鎖 / 管腔形成 / メダカ

Outline of Final Research Achievements

Intestinal atresia (IA) is one of the congenital malformation of the intestine which causes bowel obstruction. To elucidate the molecular and genetic mechanism of intestinal atresia, I analyzed medaka mutant that shows IA during embryogenesis. By positional cloning, I identified the causal gene that encode the gene involved in cytoskeletal regulation. Histochemical analysis revealed that apoptosis and epithelial-mesenchymal-transition are not in involved in IA of this mutant and abnormal accumulation of F-actin was observed in the mutant intestine. In addition, the treatment with myosin II specific inhibitor, blebbistatin, rescued IA phenotype, suggested that enhancement of actomyosin bundle formation is involved in IA in the mutant embryos.

Free Research Field

発生生物学

Academic Significance and Societal Importance of the Research Achievements

腸管閉鎖機構の研究にはこれまでモデル実験動物を利用した順遺伝学的なアプローチがなされていなかった。順遺伝学的なアプローチはこれまでの知見にとらわれない新たなメカニズムを明らかにすることが期待でき、本研究によって腸管閉鎖というヒトの先天性疾患を新しい視点から明らかにすることが期待できる。加えて、管腔形成という生物にとって非常に基本的な形態形成の機構の一端を明らかにすることも期待できる。