PTPRM基因是我们在心脏畸形胎儿遗传学诊断前瞻性研究中，应用染色体芯片技术所发现的，位于18p11.23微重复区域中，且高表达于畸形心脏组织的一个蛋白编码基因。前期发现：PTPRM拷贝数重复在心脏畸形胎儿中发生率显著高于人群携带频率；过表达PTPRM可致斑马鱼心脏发育畸形和心率下降，可显著抑制P19细胞向心肌样细胞分化，可导致P19细胞中经典Wnt信号通路基因表达显著降低。提示PTPRM很可能通过调控Wnt信号通路影响心肌分化和心脏发育。本研究拟采用心肌细胞、斑马鱼胚胎和转基因小鼠模型，深入分析PTPRM在心肌分化和心脏发育中的作用，并以Wnt信号通路为线索，论证PTPRM参与Wnt信号通路、调控心肌分化和心脏发育的具体生物学机制。阐明PTPRM微重复在胚胎心脏发育中的作用及机制，将为探索先天性心脏病的发病机制提供新思路，并为先心病的防治提供新靶标。

In our previous published study on the prospective genetic analysis of congenital heart disease fetus, we identified a novel chromosome microduplication of PTPRM (located in the 18p11.23 microduplication region) using chromosome microarray assay technology. PTPRM, a human protein-coding gene, is pathologically upregulated in myocardial tissue of fetus with congenital heart disease (CHD). The incidence of the PTPRM duplication in CHD fetus is significantly higher than that in the Asian population. Additionally, overexpression of PTPRM could not only lead to cardiac malformation in zebrafish embryos, but also significantly inhibit the cardiomyocyte differentiation of P19 cells. Taken together, our results indicated PTPRM played an important role in the canonical Wnt signaling pathway, a well-known pathway associated with heart development. Notably, we also found these canonical Wnt signaling pathway genes were down-regulated when overexpressing PTPRM in P19 cells. All these results suggested that PTPRM microduplication may affect cardimyocyte differentiation and cardiac development by regulating Wnt signaling. Therefore, we aim to investigate the role of PTPRM and the underlying mechanism in cardiac development using P19 cells, zebrafish, and mouse model. It is important to illustrate the function and mechanism of PTPRM in embryonic cardiac development, which may provide a new target for the prevention and treatment of congenital heart diseases in clinic in the future.