DISSECTING THE ROLE OF SIALOGLYCANS IN EMBRYONIC DEVELOPMENT

剖析唾液酸聚糖在胚胎发育中的作用

• 批准号: 432242332
• 负责人: Dr. Birgit Weinhold
• 金额: --
• 依托单位: Institut für Klinische Biochemie
• 依托单位国家: 德国
• 项目类别: Research Units
• 财政年份: 2019
• 资助国家: 德国
• 起止时间: 2018-12-31 至 2022-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/432242332?language=en
• 关键词: DISSECTING; ROLE; SIALOGLYCANS; EMBRYONIC; DEVELOPMENT

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.

带负电荷的糖唾液酸(SIA)在细胞表面的大部分糖链中占据最外层的位置。由于SIA激活酶CMP-唾液酸合成酶(CMAS)的遗传消融导致唾液酸聚糖的缺乏，导致了小鼠在胚胎9.5天(E9.5)前后的胚胎死亡。我们发现，Sia对于胚胎的早期发育是必不可少的，但对于孕期胎儿-母体免疫平衡，即保护同种异体移植物免受母体固有免疫系统的攻击是至关重要的。唾液酸化缺乏导致补体途径与其关键补体成分3(C3)的控制受损，导致组织炎症、破坏和胚胎死亡。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，并揭示补体调控之外的Sia功能，我们的目标是将CmAs基因敲除与C3基因敲除小鼠相结合。