视黄酸致小鼠腭裂分子机制的研究  

Molecular mechanism of cleft palate induced by retionic acid

作　　者：朱江波[1] 印木泉[1] 朱玉平[1] 陈蓉芳[1] 万旭英[1] 马玺里[1] 郭苗莉[1] 张天宝[1] 

机构地区：[1]第二军医大学卫生毒理学教研室,上海200433

出　　处：《卫生研究》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 )

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.

关 键 词：腭裂视黄酸 基因筛选 分子机制 

分 类 号：Q754[生物学—分子生物学] Q132.3