DISSECTING THE ROLE OF SIALOGLYCANS IN EMBRYONIC DEVELOPMENT

带负电荷的糖唾液酸（Sia）占据细胞表面聚糖主体的最外位置。由于Sia激活酶CMP-唾液酸合酶（CMAS）的基因消除导致的唾液酸化聚糖缺乏导致小鼠胚胎第9.5天（E9.5）左右的胚胎死亡。我们发现，Sia对胚胎的早期发育至关重要，但对妊娠期间胎儿-母体免疫稳态至关重要，即，用于保护同种异体移植物免受母体先天免疫系统的攻击。唾液酸化缺陷导致补体途径及其关键补体成分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在胎儿-母体界面影响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除了补体调节之外的Sia功能，我们的目标是将Cmas敲除与C3敲除小鼠联合收割机组合。

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.