Paranodal junction formation and spermatogenesis require sulfoglycolipids.
Mammalian sulfoglycolipids comprise two major members, sulfatide (HSO3-3-galactosylceramide) and seminolipid (HSO3-3-monogalactosylalkylacylglycerol). Sulfatide is a major lipid component of the myelin sheath and serves as the epitope for the well known oligodendrocyte-marker antibody O4. Seminolipid is synthesized in spermatocytes and maintained in the subsequent germ cell stages. Both sulfoglycolipids can be synthesized in vitro by using the isolated cerebroside sulfotransferase. To investigate the physiological role of sulfoglycolipids and to determine whether sulfatide and seminolipid are biosynthesized in vivo by a single sulfotransferase, Cst-null mice were generated by gene targeting. Cst(-/-) mice lacked sulfatide in brain and seminolipid in testis, proving that a single gene copy is responsible for their biosynthesis. Cst(-/-) mice were born healthy, but began to display hindlimb weakness by 6 weeks of age and subsequently showed a pronounced tremor and progressive ataxia. Although compact myelin was preserved, Cst(-/-) mice displayed abnormalities in paranodal junctions. On the other hand, Cst(-/-) males were sterile because of a block in spermatogenesis before the first meiotic division, whereas females were able to breed. These data show a critical role for sulfoglycolipids in myelin function and spermatogenesis.
Honke
Koichi
K
Department of Biochemistry, Osaka University Medical School, 2-2 Yamadaoka, Suita, Osaka 565-0871, Japan.
Hirahara
Yukie
Y
Dupree
Jeffrey
J
Suzuki
Kinuko
K
Popko
Brian
B
Fukushima
Kikuro
K
Fukushima
Junko
J
Nagasawa
Takashi
T
Yoshida
Nobuaki
N
Wada
Yoshinao
Y
Taniguchi
Naoyuki
N
D000818:Animals; D005700:Galactosyltransferases / Q000502:physiology; D006017:Glycolipids / Q000502:physiology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009186:Myelin Sheath / Q000473:pathology / Q000502:physiology* / Q000648:ultrastructure; D051146:N-Acylsphingosine Galactosyltransferase; D013091:Spermatogenesis; D013094:Spermatozoa / Q000473:pathology; D015238:Sulfotransferases / Q000502:physiology
D006017:Glycolipids; C011117:sulfoglycolipids; D005700:Galactosyltransferases; D051146:N-Acylsphingosine Galactosyltransferase; D015238:Sulfotransferases; C020556:galactosylceramide sulfotransferase