HOXD13、FHL1和先天性马蹄内翻足的相关研究  

Research of HOXD13 and FHL1 in idiopathic congenital talipes equinovarus

作　　者：王莉莉[1] 富伟能[1] 李增刚[1] 孙开来[1] 

机构地区：[1]中国医科大学基础医学院医学遗传学教研室,沈阳110001

出　　处：《遗传》2008年第1期46-50,共5页Hereditas（Beijing)

基　　金：国家重点基础研究发展规划(编号:2001CB510301)资助~~

摘　　要：为研究HOXD13、FHL1和先天性马蹄内翻足的关系,应用变性梯度凝胶电泳技术检测HOXD13基因在先天性马蹄内翻足个体中的突变,应用半定量RT-PCR及免疫组织化学技术检测HOXD13、FHL1在先天性马蹄内翻足患者肌肉组织中的表达;并用软件预测FHL1基因上游HOXD13的结合位点,凝胶阻滞试验(Electrophoretic mobility shift assay,EMSA)验证HOXD13和FHL1的相互作用。结果84例先天性马蹄内翻足患者中未发现HOXD13基因编码区突变存在。与同期正常足部肌肉组织相比HOXD13(33.3%),FHL1(46.6%)在先天性马蹄内翻足患者肌肉组织中表达明显下调。EMSA结果表明,当HOXD13存在时出现特异的DNA阻滞条带。上述结果说明:HOXD13的编码区突变可能不是先天性马蹄内翻足发生的原因,而HOXD13和FHL1表达水平的改变可能与马蹄内翻足畸形的发生有关,HOXD13可能通过直接调控FHL1发挥作用。To investigate the relationship of HOXD13 and FHL1 in idiopathic congenital talipes equinovarus（ICTEV）, 84 samples from patients with ICTEV were used in the study.Mutation in the coding region of HOXDI 3 was detected by denaturing gradinent electrophoresis. The mRNA and protein levels of HOXD13 and FHL1 were evaluated by RT-PCR and immunohistochemistry, respectively. The binding site of FHL1 to HOXD13 predicted by PMATCH software was validated by EMSA（ Electrophoretic mobility shift assay, EMSA）.No mutation was found in the coding region of HOXD13 in 84 samples from patients with ICTEV. Both HOXD13（33.3%） and FHLl（46.6%） were down-regulated in ICTEV muscle tissue.The result of EMSA showed that the special binding band appeared when HOXD13 existed. The results shows that HOXD13 gene mutation was not involved in outbreak in idiopathic congenital talipes equinovarus, but changes of HOXD13 and FHL1 gene expression related to the development of talipes equinovarus malformation. HOXD13 might play an role in ICTEV through regulating FHL1 expression.

关 键 词：先天性马蹄内翻足 HOXD13 FHL1 突变 表达 

分 类 号：R726.8[医药卫生—儿科]