DECIPHERING SIALIC ACID O-ACETYLATION

破译唾液酸邻乙酰化

• 批准号: 432251600
• 负责人: Privatdozentin Dr. Martina Mühlenhoff
• 金额: --
• 依托单位: Institut für Klinische Biochemie
• 依托单位国家: 德国
• 项目类别: Research Units
• 资助国家: 德国
• 项目状态: 未结题
• 来源: https://gepris.dfg.de/gepris/projekt/432251600?language=en
• 关键词: DECIPHERING; SIALIC; ACID; ACETYLATION

The aim of this proposal is to investigate the impact of sialic acid O-acetylation on kidney development and function by using novel genetic mouse models. O-Acetylation significantly contributes to the structural diversity of sialoglycans, but its function in vivo remains poorly understood. In preliminary work, we demonstrated that genetic ablation of the murine sialate O-acetyltransferase CASD1 results in a complete loss of 9-O- and 7,9-O-acetylated sialoglycans and causes a renal tubular phenotype. To understand how sialic acid O-acetylation contributes to kidney integrity, we will perform functional assays on isolated primary cells and explore the contribution of O-acetylated sialoglycans on tubular epithelial and vascular endothelial cells through the generation of cell type-specific Casd1 knockout mice. By functional assessment of rare, patient-derived CASD1 variants, we will investigate whether CASD1 is a novel candidate gene for human kidney disease. Within the research unit, our project is closely linked to projects 2, 5 and 9, and will benefit from specific interactions with projects 1, 6, and 8.

该提案的目的是通过使用新型遗传小鼠模型来研究唾液酸 O-乙酰化对肾脏发育和功能的影响。 O-乙酰化对唾液酸聚糖的结构多样性有显着贡献，但其体内功能仍知之甚少。在初步工作中，我们证明小鼠唾液酸O-乙酰转移酶CASD1的基因消除会导致9-O-和7,9-O-乙酰化唾液聚糖完全丧失，并导致肾小管表型。为了了解唾液酸 O-乙酰化如何促进肾脏完整性，我们将对分离的原代细胞进行功能测定，并通过生成细胞类型特异性 Casd1 敲除小鼠来探索 O-乙酰化唾液酸聚糖对肾小管上皮和血管内皮细胞的贡献。通过对源自患者的罕见 CASD1 变体进行功能评估，我们将研究 CASD1 是否是人类肾脏疾病的新候选基因。在研究单位内，我们的项目与项目 2、5 和 9 密切相关，并将受益于与项目 1、6 和 8 的特定互动。