title: Paranodal junction formation and spermatogenesis require sulfoglycolipids.
abstract: 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.
authors.affiliation: Department of Biochemistry, Osaka University Medical School, 2-2 Yamadaoka, Suita, Osaka 565-0871, Japan.
authors.forename: Koichi
authors.initials: K
authors.lastname: Honke
authors.forename: Yukie
authors.initials: Y
authors.lastname: Hirahara
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Dupree
authors.forename: Kinuko
authors.initials: K
authors.lastname: Suzuki
authors.forename: Brian
authors.initials: B
authors.lastname: Popko
authors.forename: Kikuro
authors.initials: K
authors.lastname: Fukushima
authors.forename: Junko
authors.initials: J
authors.lastname: Fukushima
authors.forename: Takashi
authors.initials: T
authors.lastname: Nagasawa
authors.forename: Nobuaki
authors.initials: N
authors.lastname: Yoshida
authors.forename: Yoshinao
authors.initials: Y
authors.lastname: Wada
authors.forename: Naoyuki
authors.initials: N
authors.lastname: Taniguchi
mesh_terms: 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
chemical_list: D006017:Glycolipids; C011117:sulfoglycolipids; D005700:Galactosyltransferases; D051146:N-Acylsphingosine Galactosyltransferase; D015238:Sulfotransferases; C020556:galactosylceramide sulfotransferase