Departments of Biochemistry and Human Genetics, Emory University School of Medicine, Atlanta, GA 30322, USA.
Proc Natl Acad Sci U S A. 2010 May 18;107(20):9228-33. doi: 10.1073/pnas.0914004107. Epub 2010 May 3.
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.
Cosmc 是一种分子伴侣，被认为是表达活性 T-合成酶所必需的，T-合成酶是唯一将 Tn 抗原（GalNAcalpha1-Ser/Thr-R）半乳糖基化形成核心 1 Galbeta1-3GalNAcalpha1-Ser/Thr（T 抗原）的酶，在粘蛋白型 O-聚糖生物合成过程中。在这里，我们表明，在小鼠中敲除 X 连锁的 Cosmc 基因会导致胚胎致死和 Tn 抗原表达。Cosmc 的缺失与 T-合成酶的缺失有关，但与糖蛋白生物合成所需的其他酶无关，这表明 Cosmc 在体内是 T-合成酶特有的。我们生成了具有靶向 Cosmc 缺失的基因镶嵌小鼠，存活的小鼠表现出与 Tn 抗原表达相关的异常，这些异常与几种人类疾病有关。
