Study on the pathophysiological roles of seipin, a generalized lipodystrophy causative gene product

2015 Fiscal Year Final Research Report

• Project/Area Number: 24390237
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Partial Multi-year Fund
• Section: 一般
• Research Field: Endocrinology
• Research Institution: Jichi Medical University (2014-2015); Kyoto University (2012-2013)
• Principal Investigator: Ebihara Ken 自治医科大学, 医学部, 准教授 (70362514)
• Co-Investigator(Kenkyū-buntansha): ABE MEGUMI 京都大学, 生命科学研究科, 助教 (20568688) ; KUSAKABE TORU 京都大学, 医学研究科, 准教授 (60452356)
• Project Period (FY): 2012-04-01 – 2016-03-31
• Keywords: セイピン / 脂肪萎縮症 / ラットモデル / 精神発達遅滞 / 精子低形成

Outline of Final Research Achievements

Mutations of BSCL2 cause the most severe form of congenital generalized lipodystrophy (CGL). BSCL2mRNAis highly expressed in the brain and testis in addition to the adipose tissue in human, suggesting physiological roles of seipin in non-adipose tissues. Since we found BSCL2 mRNA expression pattern among organs in rat is similar tohumanwhile it is not highly expressed in mouse brain,we generated a Bscl2/seipin knockout (SKO) rat. SKO rats showed total lack of white adipose tissues, while physiologically functional brown adipose tissuewas preserved. Besides the lipodystrophic phenotypes, SKO rats showed impairment of spatial working memory with brainweight reduction and infertility with azoospermia.We confirmed reduction of brain volume and number of sperm in human patients with BSCL2 mutation. This is the first report demonstrating that seipin is necessary for normal brain development and spermatogenesis in addition to white adipose tissue development.

Free Research Field

内分泌代謝学