Evaluation of iron-sulfur proteins in hematopoietic cells through anamorsin

2021 Fiscal Year Final Research Report

• Project/Area Number: 19K08861
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 54010:Hematology and medical oncology-related
• Research Institution: Osaka University
• Principal Investigator: Shibayama Hirohiko 大阪大学, 医学系研究科, 招へい教授 (60346202)
• Co-Investigator(Kenkyū-buntansha): 野崎 健司 大阪大学, 医学部附属病院, 医員 (00836413) ; 横田 貴史 大阪大学, 医学系研究科, 准教授 (60403200)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Keywords: アナモルシン / 鉄・硫黄クラスター / アポトーシス / 遺伝子欠損マウス / 条件付き遺伝子欠損マウス / Bリンパ球

Outline of Final Research Achievements

Anamorsin (AM) was cloned as a cell-death-defying factor. AM-deficient mice are embryonic lethal. To overcome the embryonic lethality, we generated AM conditional KO (AMflox/flox) mice. CD19-Cre/AMflox/flox mice, with AM deleted specifically in CD19+ B cells, exhibited fewer B220+ B cells in spleen, peripheral blood, and LN. CD19-Cre/AMflox/flox mice showed significantly fewer follicular type I (FO-I) cells, which are the most matured FO-B cells, and greater apoptotic cell accumulation in spleen. This suggested that AM deficiency affected terminal differentiation of B cells by increased apoptosis. Furthermore, CD19-Cre/AMflox/flox mice lacked splenic CD19+B220－/low cells. The reduction of p38MAPK, the downstream molecule of BCR signaling, in CD19-Cre/AMflox/flox mice might account for the lack of FO-I cells and splenic CD19+B220－/low cells. Overall, our results suggest that AM plays essential roles in B-cell terminal differentiation.

Free Research Field

血液内科

Academic Significance and Societal Importance of the Research Achievements

AMは鉄・硫黄（Fe-S）クラスター形成に関与する分子であることが明らかとなっている。Fe-Sクラスター蛋白は遺伝子の発現制御、DNA修復、光合成などのエネルギー代謝など様々な細胞機能に関与していることが知られているが、Fe-Sクラスター形成がB細胞の成熟分化に関連している報告はこれまでなく、今回の発見は興味深いものと考える。