DISSECTING THE ROLE OF SIALOGLYCANS IN EMBRYONIC DEVELOPMENT

带负电荷的糖唾液酸（Sia）在大部分细胞表面聚糖中占据最外层的位置。由于sia激活酶cmp -唾液酸合成酶（CMAS）的基因消蚀，导致小鼠在胚胎第9.5天（E9.5）左右出现胚胎致死。我们发现，Sia对于胚胎的早期发育是必不可少的，但对于怀孕期间胎儿-母体免疫稳态至关重要，即保护同种异体移植物免受母体先天免疫系统的攻击。唾液酸缺乏导致补体通路及其关键补体成分3 （C3）的控制受损，导致组织炎症、破坏和胚胎致死。Cmas模型将允许定义Sia影响胎儿-母体界面补体系统的确切分子机制。为了克服C3介导的胚胎致死性，并揭示Sia除补体调节外的功能，我们的目标是将Cmas敲除与C3敲除小鼠结合起来。

The negatively charged sugar sialic acid (Sia) occupies the outermost position in the bulk of cell surface glycans. Lack of sialylated glycans due to genetic ablation of the Sia-activating enzyme CMP-sialic acid synthase (CMAS) resulted in embryonic lethality around embryonic day 9.5 (E9.5) in mice. We showed that Sia is dispensable for early development of the embryo proper but pivotal for fetal-maternal immune homeostasis during pregnancy, i.e., for protecting the allograft implant against attack by the maternal innate immune system. Sialylation-deficiency resulted in impaired control of the complement pathway with its key complement component 3 (C3), causing tissue inflammation, destruction, and embryonic lethality. The Cmas model will allow defining the exact molecular mechanisms by which Sia impacts the complement system at the fetal-maternal interface. To overcome C3-mediated embryonic lethality and to uncover Sia functions apart from complement regulation we aim to combine the Cmas knockout with a C3 knockout mouse.