摘要
目的 探讨化学物致小鼠腭裂的分子机制。方法 以视黄酸 (RA)为受试物 ,采用抑制消减杂交技术 (SSH)从全基因组水平上对RA致腭裂相关差异表达基因进行筛选。结果 得到RA逆向差异表达片断14个 ,正向差异表达片断 9个。经测序和GeneBank比对后得到已知基因 7条 ,余者为未知功能基因或未知基因。结论 Gpc3和胰岛素诱导蛋白 1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。还可能影响细胞对营养物质的摄取而引起Rps2 5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 the molecular mechanism of cleft palate induced by chemicals. Methods Retionic acid was used as a known teratogen to induc e cleft palate in ICR mice and a suppression subtractive hybridization (SSH) technique was applied to identify differentially expressed genes that related to cleft palate of ICR mice.Results 14 reverse differently and 9 forward differentially expressed clones were obtained. Some clones were selected to be sequenced and aligned to GeneBank.Conclusion In this study, suppressed Gpc3 and Insulin-Induced protein 1 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. Tn C could bind to Ptprs and Gpcs, and HSPGs were ligands for Ptrps. Up-regulate of Rps25 might play a role in cleft palate by excessively apoptosis.
出处
《卫生研究》
CAS
CSCD
北大核心
2004年第6期690-693,共4页
Journal of Hygiene Research
基金
国家自然科学基金资助项目 (No .30 0 70 662 )
国家重点基础研究规划 ("973"计划
No.2 0 0 2C1 351 2 90 1 )
关键词
腭裂视黄酸
基因筛选
分子机制
cleft-palate, retionic acid, gene screen, molecular mechanism
