RRC ID 12722
Author Nishie T, Hikimochi Y, Zama K, Fukusumi Y, Ito M, Yokoyama H, Naruse C, Ito M, Asano M.
Title Beta4-galactosyltransferase-5 is a lactosylceramide synthase essential for mouse extra-embryonic development.
Journal Glycobiology
Abstract 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 beta4-galactosyltransferase-6 (beta4GalT-6) gene in the rat brain. However, the existence of another LacCer synthase gene was shown in cultured cells lacking beta4GalT-6. Here, we report that LacCer synthase is mainly synthesized by the beta4GalT-5 gene during early mouse embryogenesis, and its disruption is embryonic lethal. beta4GalT-5-deficient embryos showed developmental retardation from E7.5 and died by E10.5 as reported previously. LacCer synthase activity was significantly reduced in beta4GalT-5-deficient embryos and extra-embryonic endoderm (XEN) cells derived from blastocysts, and it was recovered when beta4GalT-5 cDNA was introduced into beta4GalT-5-deficient XEN cells. The amounts of LacCer and GM3 ganglioside were drastically reduced, while GlcCer accumulated in the beta4GalT-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. beta4GalT-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 beta4GalT-5 is essential for extra-embryonic development during early mouse embryogenesis.
Volume 20(10)
Pages 1311-22
Published 2010-10-1
DOI 10.1093/glycob/cwq098
PII cwq098
PMID 20574042
MeSH Animals Antigens, CD / metabolism Blastocyst / metabolism Cells, Cultured Embryo, Mammalian / cytology* Embryo, Mammalian / metabolism Embryonic Development* Endoderm / physiology* Extraembryonic Membranes / metabolism* Female G(M3) Ganglioside / metabolism Galactosyltransferases / metabolism* Galactosyltransferases / physiology* Genes, Lethal Giant Cells / metabolism Giant Cells / pathology Glycosphingolipids Hematoma / etiology Hematoma / metabolism Hematoma / pathology Humans In Situ Hybridization Lactosylceramides / metabolism Lentivirus / genetics Male Mice Mice, Inbred C57BL Mice, Inbred ICR Mice, Knockout Mice, Transgenic Tetraploidy Trophoblasts / metabolism Trophoblasts / pathology
IF 4.06
Times Cited 34
DNA material CS-CA-MCS (RDB05963) pCAG-HIVgp (RDB04394) pCMV-VSV-G-RSV-Rev (RDB04393)