Deciphering the function for S1P transporter, Spns2, in mammals

2014 Fiscal Year Final Research Report

• Project/Area Number: 24370084
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Partial Multi-year Fund
• Section: 一般
• Research Field: Cell biology
• Research Institution: National Cardiovascular Center Research Institute
• Principal Investigator: MOCHIZUKI Naoki 独立行政法人国立循環器病研究センター, 研究所, 部長 (30311426)
• Co-Investigator(Kenkyū-buntansha): NAKAJIMA Hiroyuki 国立循環器病研究センター, 研究所, 研究員 (10467657)
• Co-Investigator(Renkei-kenkyūsha): FUKUHARA Shigetomo 国立循環器病研究センター, 研究所, 室長 (70332880)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Keywords: スフィンゴシン１燐酸 / ノックアウトマウス / 輸送体 / リンパ球 / 胸腺 / 骨髄

Outline of Final Research Achievements

We had identified Spns2 as a S1P transporter in zebrafish. Therefore, we aimed at studying the function of Spns2 in mammals in S1P signaling.
First, we developed global Spns2 knockout (KO) mice and analyzed the number of lymphocytes in primary and secondary lymphatic organs, because S1P is known to be essential for egress from the primary lymphatic organs. Mature T- and B- lymphocytes in the blood were decreased. Mature T-lymphocytes were accumulated in the thymus. Consistently, the number of mature T-lymphocytes was decreased in the secondary lymphatic organs. Similarly, the number of mature B-lymphocytes in the bone marrow and the secondary lymphatic organs was decreased, suggesting that the egress of T- and B-lymphocytes were decreased. The endothelium-specific Spns2 KO mice exhibited the similar phenotype found in global KO mice. These data indicate that endothelial Spns2 functions as a S1P transporter to induce the egress of lymphocytes from the primary lumphatic organs.

Free Research Field

循環器発生・細胞生物学