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 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.
Department of Medicine and Clinical Science.
Chihiro
C
Ebihara
Department of Medicine and Clinical Science, Institute for Advancement of Clinical and Translational Science, Kyoto University Hospital, Kyoto, Japan kebihara@jichi.ac.jp.
Ken
K
Ebihara
Department of Medicine and Clinical Science, Institute for Advancement of Clinical and Translational Science, Kyoto University Hospital, Kyoto, Japan.
Megumi
M
Aizawa-Abe
Institute of Laboratory Animals.
Tomoji
T
Mashimo
Department of Medicine and Clinical Science.
Tsutomu
T
Tomita
Department of Medicine and Clinical Science.
Mingming
M
Zhao
Department of Medicine and Clinical Science.
Valentino
V
Gumbilai
Department of Medicine and Clinical Science, Medical Innovation Center.
Toru
T
Kusakabe
Department of Medicine and Clinical Science.
Yuji
Y
Yamamoto
Department of Medicine and Clinical Science, Medical Innovation Center.
Daisuke
D
Aotani
Department of Medicine and Clinical Science.
Sachiko
S
Yamamoto-Kataoka
Department of Medicine and Clinical Science.
Takeru
T
Sakai
Department of Medicine and Clinical Science, Institute for Advancement of Clinical and Translational Science, Kyoto University Hospital, Kyoto, Japan Department of Health and Science, Kyoto University Graduate School of Medicine, Kyoto 6068507, Japan and.
Kiminori
K
Hosoda
Institute of Laboratory Animals.
Tadao
T
Serikawa
Department of Medicine and Clinical Science, Medical Innovation Center.
Kazuwa
K
Nakao
D050156:Adipogenesis / Q000235:genetics*; D000818:Animals; D001921:Brain / Q000254:growth & development* / Q000378:metabolism; D044388:GTP-Binding Protein gamma Subunits / Q000096:biosynthesis / Q000235:genetics*; D018507:Gene Expression Regulation, Developmental; D055786:Gene Knockout Techniques; D006801:Humans; D008297:Male; D051379:Mice; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D013091:Spermatogenesis / Q000235:genetics*; D013094:Spermatozoa / Q000254:growth & development / Q000378:metabolism; D013737:Testis / Q000254:growth & development / Q000378:metabolism
C432679:BSCL2 protein, human; D044388:GTP-Binding Protein gamma Subunits; D012333:RNA, Messenger