Molecular genetics of neurocristopathy

Ncx基因属于Hox 11同源盒家族基因，在神经嵴来源的组织中特异性表达。Ncx/Hox11L.1缺陷（Ncx-KO）小鼠具有肠神经节中神经元细胞数量增加的巨结肠。(1)在Ncx缺陷小鼠中肠神经节中的神经元细胞死亡受损，导致神经元细胞数量增加。在Ncx缺陷小鼠的肠神经丛中发现了人类肠神经元发育异常的典型表现（AchE组织化学上粘膜和肌肉层中的异位神经节，NADPH黄递酶组织化学上的幽灵样神经节）。（2）Ncx-KO小鼠膀胱神经节中神经元细胞数量多于对照组。腹腔注射一氧化氮合酶（NOS）抑制剂可使Ncx-KO小鼠膀胱测压图中的阈值压力和剩余压力升高至对照水平。膀胱神经节中神经元细胞数量的增加诱导Ncx-KO小鼠膀胱尿道括约肌功能障碍。膀胱神经细胞中一氧化氮的含量对于控制膀胱尿道括约肌的功能很重要。(3)在使用来自野生型和Ncx缺陷小鼠的肠神经元cDNA的RDA方法的过程中，我们获得了新的kelch家族基因，并命名为Nd 1（Ncx下游基因1）。我们正在通过创建转基因和基因敲除小鼠来表征Nd 1在体内的功能。

The Ncx gene which belongs to the Hox11 homeobox family gene specifically expressed in neural crest derived tissues. Ncx/Hox11L.1-deficient (Ncx-KO) mice have a megacolon with an increased number of neuronal cells in the enteric ganglia. (1) Neuronal cell death in enteric ganglia is impaired in Ncx deficient mice resulting in an increased number of neuronal cells. Typical findings of human intestinal neuronal dysplasia (ectopic ganglia, in the mucosal and muscular layers on AchE histochemistry, ghost-like ganglia on NADPH diaphorase histochemistry) were foung in enteric plexus of Ncx deficient mice. (2)Neuronal cells were more numerous in vesical ganglia from Ncx-KO mice than in ganglia from controls. The intraperitoneal injection of an inhibitor of nitric oxide synthase (NOS) increased the threshold pressure and the remaining pressure in cystometrograms from Ncx-KO mice to the control level. The increased number of neuronal cells in vesical ganglia induces dysfunction of vesico-urethral sphincter muscle in Ncx-KO mice. The amount of nitric oxide in vesical nerve cells is important to control function of the vesico-urethral sphincter muscle. (3) During a process of a RDA method using enteric neuron cDNAs from wild type and Ncx-deficient mice, we obtained novel kelch family gene and named Nd1(Ncx downstream gene 1 ). We are characterizing a function of Nd1 in vivo by creating transgenic and knockout mice.