Seipin is necessary for normal brain development and spermatogenesis in addition to adipogenesis

Seipin, encoded by BSCL2 gene, is a protein whose physiological functions remain unclear. Mutations of BSCL2 cause the mostsevere form of congenital generalized lipodystrophy (CGL).BSCL2mRNAis highlyexpressedin thebrain and testis in addition to the adipose tissue in human, suggesting physiological roles of seipin in non-adipose tissues. Since we found BSCL2 mRNA expressionpatternamongorgansinratissimilartohumanwhileitisnothighlyexpressedinmousebrain,wegeneratedaBscl2/ seipin knockout (SKO) rat using the method with ENU (N-ethyl-N-nitrosourea) mutagenesis. SKO rats showed total lackof white adipose tissues including mechanical fat such as bone marrow and retro-orbital fats, while physiologically functional brown adipose tissuewas preserved. Besidesthe lipodystrophic phenotypes, SKO rats showed impairment of spatial working memory with brain weight reduction and infertility with azoospermia. We confirmed reduction of brain volume and numberof 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.