Cosmc is an essential chaperone for correct protein O-glycosylation.

Cosmc is a molecular chaperone thought to be required for expression of active T-synthase, the only enzyme that galactosylates the Tn antigen (GalNAcalpha1-Ser/Thr-R) to form core 1 Galbeta1-3GalNAcalpha1-Ser/Thr (T antigen) during mucin type O-glycan biosynthesis. Here we show that ablation of the X-linked Cosmc gene in mice causes embryonic lethality and Tn antigen expression. Loss of Cosmc is associated with loss of T-synthase but not other enzymes required for glycoprotein biosynthesis, demonstrating that Cosmc is specific in vivo for the T-synthase. We generated genetically mosaic mice with a targeted Cosmc deletion and survivors exhibited abnormalities correlated with Tn antigen expression that are related to several human diseases.