論文

査読有り
2010年10月

β4-Galactosyltransferase-5 is a lactosylceramide synthase essential for mouse extra-embryonic development

Glycobiology
  • Toshikazu Nishie
  • ,
  • Yoko Hikimochi
  • ,
  • Kota Zama
  • ,
  • Yoshiyasu Fukusumi
  • ,
  • Mitutoshi Ito
  • ,
  • Haruka Yokoyama
  • ,
  • Chie Naruse
  • ,
  • Makoto Ito
  • ,
  • Masahide Asano

20
10
開始ページ
1311
終了ページ
1322
記述言語
英語
掲載種別
研究論文(学術雑誌)
DOI
10.1093/glycob/cwq098

Glycosphingolipids (GSLs) are important for various biological functions in the nervous system, the immune system, embryogenesis and in other tissues and processes. Lactosylceramide (LacCer), which is synthesized from glucosylceramide (GlcCer) by LacCer synthase, is a core structure of GSLs, including gangliosides. LacCer synthase was reported to be synthesized by the β4-galactosyltransferase-6 (β4GalT-6) gene in the rat brain. However, the existence of another LacCer synthase gene was shown in cultured cells lacking β4GalT-6. Here, we report that LacCer synthase is mainly synthesized by the β4GalT-5 gene during early mouse embryogenesis, and its disruption is embryonic lethal. β4GalT-5-deficient embryos showed developmental retardation from E7.5 and died by E10.5 as reported previously. LacCer synthase activity was significantly reduced in β4GalT-5-deficient embryos and extra-embryonic endoderm (XEN) cells derived from blastocysts, and it was recovered when β4GalT-5 cDNA was introduced into β4GalT-5-deficient XEN cells. The amounts of LacCer and GM3 ganglioside were drastically reduced, while GlcCer accumulated in the β4GalT-5- deficient XEN cells. Hematoma and ectopically accumulated trophoblast giant cells were observed in the anti-mesometrial pole of the extra-embryonic tissues, although all three embryonic layers formed. β4GalT-5-deficient embryos developed until E12.5 as chimeras with wild-type tetraploid cells, which formed the extra-embryonic membranes, indicating that extra-embryonic defects caused the early embryonic lethality. Our results suggest that β4GalT-5 is essential for extra-embryonic development during early mouse embryogenesis. © 2010 The Author.

リンク情報
DOI
https://doi.org/10.1093/glycob/cwq098
PubMed
https://www.ncbi.nlm.nih.gov/pubmed/20574042
ID情報
  • DOI : 10.1093/glycob/cwq098
  • ISSN : 0959-6658
  • ISSN : 1460-2423
  • PubMed ID : 20574042
  • SCOPUS ID : 77956520108

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