Impairment of embryonic cell division and glycosaminoglycan biosynthesis in glucuronyltransferase-I-deficient mice.
We have revealed that in Caenorhabditis elegans, non-sulfated chondroitin is required for normal cell division and cytokinesis at an early developmental stage, whereas heparan sulfate is essential for embryonic morphogenesis in the later stages of development. To clarify the roles of chondroitin sulfate and heparan sulfate in early embryogenesis in mammals, we generated glucuronyltransferase-I (GlcAT-I) knock-out mice by gene targeting. GlcAT-I is an enzyme required for the synthesis of both chondroitin sulfate and heparan sulfate. Here we report that mice with a deletion of GlcAT-I showed remarkable reduction of the synthesis of chondroitin sulfate and heparan sulfate and embryonic lethality before the 8-cell stage because of failed cytokinesis. In addition, treatment of wild-type 2-cell embryos with chondroitinase ABC had marked effects on cell division, although many heparitinase-treated embryos normally developed to blastocysts. Taken together, these results suggest that chondroitin sulfate in mammals, as with non-sulfated chondroitin in C. elegans, is indispensable for embryonic cell division.
Izumikawa
Tomomi
T
Department of Biochemistry, Kobe Pharmaceutical University, Higashinada-ku, Kobe 658-8558, Japan.
Kanagawa
Nao
N
Watamoto
Yukiko
Y
Okada
Megumi
M
Saeki
Mika
M
Sakano
Masahiro
M
Sugahara
Kazuyuki
K
Sugihara
Kazushi
K
Asano
Masahide
M
Kitagawa
Hiroshi
H
D000818:Animals; D001483:Base Sequence; D017173:Caenorhabditis elegans / Q000166:cytology / Q000196:embryology / Q000378:metabolism; D002455:Cell Division / Q000502:physiology*; D002809:Chondroitin Sulfates / Q000096:biosynthesis; D002970:Cleavage Stage, Ovum / Q000166:cytology* / Q000378:metabolism*; D003433:Crosses, Genetic; D048749:Cytokinesis / Q000502:physiology; D017931:DNA Primers / Q000235:genetics; D046149:Embryo Culture Techniques; D047108:Embryonic Development / Q000502:physiology; D005260:Female; D014453:Glucuronosyltransferase / Q000172:deficiency* / Q000235:genetics / Q000378:metabolism; D006025:Glycosaminoglycans / Q000096:biosynthesis*; D006497:Heparan Sulfate / Q000096:biosynthesis; D006579:Heterozygote; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D013045:Species Specificity
D002809:Chondroitin Sulfates; D017931:DNA Primers; D014453:Glucuronosyltransferase; D006025:Glycosaminoglycans; D006497:Heparan Sulfate; C067806:glucuronyltransferase GlcAT-1