甲基亚硝基胍致小鼠腭裂的分子机制

The molecular mechanism of cleft palate induced by MNNG

目的探讨小鼠腭裂发生的分子机制。方法以甲基亚硝基胍(MNNG)为受试物诱导腭裂动物模型,采用抑制消减杂交技术从全基因组水平上对MNNG致腭裂相关差异表达基因进行筛选。结果得到MNNG逆向表达片断27个,正向差异表达片断14个。经测序和GeneBank比对后得到已知基因9条,余者为未知功能基因或未知基因。结论Gpc3可能通过调节腭发生过程中某些基因干扰间充质细胞正常增殖;Ptprs的表达抑制影响了某种腭突发生中细胞信号转导通路;腱生蛋白的抑制表达可能使细胞粘连力的去除失败或者由于基质中MMPs的表达降低而使腭中缝消除受阻;抑或由EgfrPtprsTnC协同作用而导致腭裂发生。还可能影响细胞对营养物质的摄取而引起Rps25的上调诱发过度的细胞凋亡而在腭裂发生中发挥作用。

Objective To explore molecular mechanism of formation of cleft palate in ICR mice. Method N-methyl-N＇-nitro-N-nitrosoguanidine（MNNG） was used as a known teratogen to induce cleft palate in ICR mice and a suppression subtractive hybridization （SSH） technique was applied to identify differentially expressed genes which related to cleft palate in ICR mice. Results 27 reverse and 15 forward differentially expressed clones were obtained. Some clones were selected to be sequenced analysis and aligned to GeneBank. Conclusion In this study, suppressed Gpe3 and Insulin-induced proteinl could affect growth of palate shelves and resulted in cleft palate by reducing the size of the palate shelves. Down-regulation of Ptprs interfered with a cell signal pathway and down-regulation of Tn C inhibited the cell de-adhesion and expression of Egfr, then suppressed Egfr prevented the normal expression of MMPs that influenced the medial edge epithelium discruption and caused cleft palate. Up-regulation of Rps25 might play a role in cleft palate by excessively apoptosis.