脐膨出是先天性腹壁发育不全导致腹腔脏器在脐环处脱出的畸形，严重危急患儿的生存和健康。其病理机制尚不清楚。MYPT1是肌球蛋白磷酸酶MLCP的靶向调节亚基，介导其催化亚基PP1c对底物肌球蛋白调节轻链RLC进行脱磷酸。我们前期通过建立MYPT1两个磷酸化位点单点突变（T694A和T852A）和双点突变（DM）的小鼠模型，首次发现：100% T694A 和DM杂合子，以及57.1% T852A 纯合子小鼠均有脐膨出表型。我们曾发现：该突变导致平滑肌中MLCP活性增高, RLC磷酸化降低。根据以往报道和前期研究数据，我们提出：腹壁发育过程中, MYPT1可能通过该两位点的磷酸化调控MLCP活性,介导细胞骨架运动,调节细胞迁移。因此，本项目将研究MYPT1突变引发脐膨出的机制并探讨其临床相关性。本课题的完成，将丰富对脐膨出病理机制的认识，并为该疾病的诊断和防治新途径以及试管婴儿的筛选提供实验依据。

Omphalocele is a defect of the abdominal wall. Neonatus with omphalocele show abdominal organs prolapse outside abdominal wall, threatening their lives. However, the pathogenesis is largely unknown. MYPT1 (myosin phosphatase targeting subunit-1), a targeting subunit of MLCP (myosin light chain phosphatase), mediates RLC (myosin regulatory light chain) dephosphorylation by catalytic subunit PP1c. We previously established three mouse models with alanine substitution at phosphorylation sites T694 and T852 of MYPT1 individually and simultaneously (double mutant, DM) and found 100% of T694A and DM heterozygous and 57.1% of T852A homozygous are with omphalocele phenotype. We also found enhanced MLCP activity and decreased RLC phosphorylation after MYPT1 mutation in smooth muscle. Based on previous reports and our preliminary research data, we propose: MYPT1 may function as a regulator of MLCP activity via T694 and T852 phosphorylation, involved in cytoskeletal movement based cell migration during abdominal wall development. Our study will provide significant insights into the molecular mechanisms of MYPT1 mutation in omphalocele and its clinical relevance.