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Seipin, encoded by  BSCL2  gene, is a protein whose physiological functions remain unclear. Mutations of  BSCL2  cause the most-severe form of congenital generalized lipodystrophy (CGL).  BSCL2  mRNA is 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 to human while it is not highly expressed in mouse brain, we generated a  Bscl2 /seipin knockout (SKO) rat using the method with ENU ( N -ethyl- N -nitrosourea) mutagenesis. SKO rats showed total lack of white adipose tissues including mechanical fat such as bone marrow and retro-orbital fats, while physiologically functional brown adipose tissue was preserved. Besides the 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 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.

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