Impairment of Embryonic Cell Division and Glycosaminoglycan Biosynthesis in Glucuronyltransferase-I-deficient Mice

Overview

Journal J Biol Chem

Specialty Biochemistry

Date 2010 Feb 19

PMID 20164174

Citations 41

Authors

Tomomi Izumikawa

Nao Kanagawa

Yukiko Watamoto

Megumi Okada

Mika Saeki

Masahiro Sakano

Kazuyuki Sugahara

Kazushi Sugihara

Masahide Asano

Hiroshi Kitagawa

Affiliations

Soon will be listed here.

Abstract

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.

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