Sialylation is essential for early development in mice.
Sialic acids are widely expressed as terminal carbohydrates on glycoconjugates of eukaryotic cells. Sialylation is crucial for a variety of cellular functions, such as cell adhesion or signal recognition, and regulates the biological stability of glycoproteins. The key enzyme of sialic acid biosynthesis is the bifunctional UDP-N-acetylglucosamine-2-epimerase/N-acetylmannosamine kinase (UDP-GlcNAc 2-epimerase), which catalyzes the first two steps of sialic acid biosynthesis in the cytosol. We report that inactivation of the UDP-GlcNAc 2-epimerase by gene targeting causes early embryonic lethality in mice, thereby emphasizing the fundamental role of this bifunctional enzyme and sialylation during development. The need of UDP-GlcNAc 2-epimerase for a defined sialylation process is exemplified with the polysialylation of the neural cell adhesion molecule in embryonic stem cells.
Schwarzkopf
Martina
M
Institut für Molekularbiologie und Biochemie, Fachbereich Humanmedizin, Freie Universität Berlin, Arnimallee 22, D-14195 Berlin-Dahlem, Germany.
Knobeloch
Klaus-Peter
KP
Rohde
Elvira
E
Hinderlich
Stephan
S
Wiechens
Nicola
N
Lucka
Lothar
L
Horak
Ivan
I
Reutter
Werner
W
Horstkorte
Rüdiger
R
D000483:Alleles; D000818:Animals; D015139:Blotting, Southern; D015153:Blotting, Western; D002238:Carbohydrate Epimerases / Q000737:chemistry* / Q000235:genetics*; D002241:Carbohydrates / Q000737:chemistry*; D002384:Catalysis; D004622:Embryo, Mammalian / Q000166:cytology; D029968:Escherichia coli Proteins; D005434:Flow Cytometry; D018390:Gene Targeting; D005838:Genotype; D006579:Heterozygote; D006720:Homozygote; D051379:Mice; D008954:Models, Biological; D008957:Models, Genetic; D011233:Precipitin Tests; D011485:Protein Binding; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012794:Sialic Acids / Q000737:chemistry*; D013234:Stem Cells; D013997:Time Factors
D002241:Carbohydrates; D029968:Escherichia coli Proteins; D012794:Sialic Acids; D002238:Carbohydrate Epimerases; C100033:UDP acetylglucosamine-2-epimerase; C083982:wecB protein, E coli