Kusafuka T, Puri P
Children's Research Centre, Our Lady's Hospital for Sick Children, Crumlin, Dublin, Ireland.
J Pediatr Surg. 1997 Apr;32(4):600-4. doi: 10.1016/s0022-3468(97)90716-8.
The RET proto-oncogene is a major cause of Hirschsprung's disease (HD) as demonstrated by the experimentally produced intestinal aganglionosis in mice with a null mutation of this gene and by the increased evidence of RET mutations in patients with HD. To evaluate the possible implication of the RET gene for the development of HD, we examined mRNA expression level of the RET gene in the bowel specimen of seven HD patients by using the reverse transcription-polymerase chain reaction technique. A significantly less intense signal for RET mRNA was found in the aganglionic bowel compared with the ganglionic bowel. In the hypoganglionic transitional zone, the RET mRNA level was higher than that of an aganglionic segment but lower than that observed in the ganglionic portion. In two patients where semiquantitative analysis was performed, the RET mRNA level in the aganglionic bowels was estimated to be approximately 1/500 of that in the ganglionic bowels. Because expression of RET mRNA plays an important role in establishing the enteric neuronal lineage, decreased RET mRNA expression in the aganglionic bowel may suggest maldevelopment of neural crest-derived cells in Hirschsprung's disease.
RET原癌基因是先天性巨结肠症（HD）的主要病因，这一点已通过该基因发生无效突变的小鼠实验性产生的肠道神经节缺失症得以证明，并且HD患者中RET突变的证据也越来越多。为了评估RET基因在HD发生发展中的可能作用，我们运用逆转录-聚合酶链反应技术检测了7例HD患者肠标本中RET基因的mRNA表达水平。与有神经节的肠段相比，无神经节的肠段中RET mRNA的信号强度明显较弱。在神经节较少的过渡区，RET mRNA水平高于无神经节段，但低于有神经节部分。在进行了半定量分析的2例患者中，无神经节肠段中的RET mRNA水平估计约为有神经节肠段的1/500。由于RET mRNA的表达在建立肠神经元谱系中起重要作用，无神经节肠段中RET mRNA表达降低可能提示先天性巨结肠症中神经嵴衍生细胞发育异常。
