Hatano M, Aoki T, Dezawa M, Yusa S, Iitsuka Y, Koseki H, Taniguchi M, Tokuhisa T
Division of Developmental Genetics, Chiba University School of Medicine, Chiba 260, Japan.
J Clin Invest. 1997 Aug 15;100(4):795-801. doi: 10.1172/JCI119593.
The Ncx/Hox11L.1 gene, a member of the Hox11 homeobox gene family, is mainly expressed in neural crest-derived tissues. To elucidate the role of Ncx/Hox11L.1, the gene has been inactivated in embryonic stem cells by homologous recombination. The homozygous mutant mice were viable. These mice developed megacolon with enteric ganglia by age 3-5 wk. Histochemical analysis of the ganglia revealed that the enteric neurons hyperinnervated in the narrow segment of megacolon. Some of these neuronal cells degenerated and neuronal cell death occurred in later stages. We propose that Ncx/Hox11L.1 is required for maintenance of proper functions of the enteric nervous system. These mutant mice can be used to elucidate a novel pathogenesis for human neuronal intestinal dysplasia.
Ncx/Hox11L.1基因是Hox11同源框基因家族的成员之一，主要在神经嵴衍生组织中表达。为了阐明Ncx/Hox11L.1的作用，该基因已通过同源重组在胚胎干细胞中失活。纯合突变小鼠能够存活。这些小鼠在3至5周龄时出现伴有肠神经节的巨结肠。对神经节的组织化学分析显示，在巨结肠的狭窄段肠神经元过度支配。其中一些神经元细胞发生退化，后期出现神经元细胞死亡。我们认为Ncx/Hox11L.1是维持肠神经系统正常功能所必需的。这些突变小鼠可用于阐明人类神经元性肠发育异常的新发病机制。
