α-DG病是α抗肌萎缩相关糖蛋白(α-DG)氧位糖基化缺陷所致的一组疾病，表现为肌营养不良和脑结构畸形，具临床和遗传异质性。在前基金支持下，我们发现α-DG病之一的福山型先天性肌营养不良(FCMD)的基因产物fukutin与靶蛋白α-DG氧位糖基化相关糖基转移酶之一POMGnT1形成复合体，并调节其酶活性，推测fukutin起分子伴侣作用，并证实另一α-DG病相关氧位糖基转移酶LARGE也定位于高尔基体。本课题拟利用FCMD患者皮肤成纤维细胞和肌活检组织标本以及体外转基因细胞模型，结合免疫荧光染色、免疫共沉淀和质谱分析等，研究fukutin与LARGE是否结合，是否对LARGE的酶活性具调节作用，由此探索fukutin影响酶产物α-DG氧位糖基化和配体结合活性的机制，揭示fukutin分子伴侣作用及其与α-DG氧位糖基化的关系。这不仅为研究该类疾病的发病机制提供线索，对治疗也可能开辟新途径

Dystroglycanopathy is a group of muscular dystrophies with a reduction in α-dystroglycan (α-DG)’ ligand-binding capacity resulting from its aberrant O-glycosylation, which has clinical and genetic heterogeneity, manifested with muscular dystrophy, brain and eye abnormalities. The exact glycan synthesis and modification pathways involved, as well as their role in ligand binding, remain only partially characterized. Among them, the function of Fukuyama type congenital muscular dystrophy(FCMD)’s gene product-fukutin, remains unknown. Under the previous grants of National Natural Science Foundation of China (30600683，81271400), we firstly reported FCMD patient out side of Japan in the world.We have demonstrated that fukutin forms a complex with muscle-eye-brain disease’s gene product-O-linked mannose 1, 2-N-acetylglucosaminyltransferase 1 (POMGnT1) and may modulate its enzymatic activity. So we speculate fukutin act as a chaparon function. We also confirmed another glycosyltransferase LARGE loclized on Glogi. Based on the early work, we want to use FCMD patient’s fibroblast, biopsied muscle and in vitro transgenic cell model, using immunofluorescence staining, co-immunoprecipitation and mass spectrometry analysis to study the relationship between fukutin and LARGE and whether fukutin modulates LARGE's enzyme activity or not, in order to investigate their interaction and influence to α-DG ligand-binding activity. This can not only provide some clues to the pathogenesis of α-dystroglycanopathy, but also develop some new path to the therapy.