• Search Research Projects
  • Search Researchers
  • How to Use
  1. Back to project page

2018 Fiscal Year Final Research Report

Elucidation of Zfat function in fetal erythropoiesis using a conditional knockout mouse

Research Project

  • PDF
Project/Area Number 15K08166
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field General anatomy (including histology/embryology)
Research InstitutionFukuoka University

Principal Investigator

DOI Keiko  福岡大学, 医学部, 講師 (10341538)

Research Collaborator Shirasawa Senji  
Tsunoda Toshiyuki  
Koyanagi Midori  
Project Period (FY) 2015-04-01 – 2019-03-31
Keywords赤血球 / 転写因子
Outline of Final Research Achievements

ZFAT, originally identified as a candidate susceptibility gene for autoimmune thyroid disease, has been reported to be involved in primitive hematopoiesis and T cell development. However, whether or not Zfat is involved in definitive erythropoiesis in the fetal liver during mammalian development remains unknown. Here, we analyzed the role of Zfat during mouse fetal erythropoiesis in the fetal liver using tamoxifen-inducible CreERT2 Zfat-deficient mice. Zfat-deficient mice exhibit moderate anemia with small and pale fetal liver through a decreased number of erythroblasts by E12.5. The apoptosis sensitivity in fetal liver erythroid progenitors was enhanced by Zfat-deficiency ex vivo. Moreover, Zfat knockdown partially inhibited the CD71-/lowTer119- to CD71highTer119- transition of fetal liver erythroid progenitors with the impairment in the elevation of CD71 expression. These results thus demonstrate that Zfat plays a critical role for erythropoiesis in the fetal liver.

Free Research Field

細胞生物学

Academic Significance and Societal Importance of the Research Achievements

本研究でのマウス個体におけるZFATの機能的役割を解明するアプローチは、ZFATの重要な機能制御ネットワークを明らかにすることが予想され、また生命維持機構における重要な転写制御ネットワークにおいて新たな知見を付加することが期待される。また、コンディショナルZFAT欠損マウスの表現型解析からは、胎児発生期の血球系分化におけるZFATの機能的役割が解明できることが予想され、免疫系の制御機構の破綻に起因する自己免疫疾患を含む免疫関連疾患とZFATの機能的役割との関連性から病因・病態の解明、さらには創薬ターゲットの探索による先駆的な治療法の開発への応用へ繋げることが期待される。

URL: 

Published: 2020-03-30  

Information User Guide FAQ News Terms of Use Attribution of KAKENHI

Powered by NII kakenhi