Molecular genetics of neurocristopathy

神经嵴病的分子遗传学

基本信息

批准号：
12470033
负责人：
HATANO Masahiko
金额：
$ 5.44万
依托单位：
Chiba University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B)
财政年份：
2000
资助国家：
日本
起止时间：
2000 至 2001
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-12470033/
关键词：
Ncx Hox11L1 Neural crest cells Intestinal neuronal dysplasia Knockout mice Transcription factor Intestinal neuronal dysplasia 腸管神経節膀胱神経節 Yeast one hybrid

项目摘要

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.

属于在神经rest衍生的组织中专门表达的Hox11同源基因基因的NCX基因。 NCX/HOX11L.1缺陷型（NCX-KO）小鼠具有肠神经节中神经元细胞数量增加的巨麦龙。（1）NCX缺乏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。人类肠道神经元发育不良的典型发现（异位神经节，在ACHE组织化学上的粘膜和肌肉层中，NADPH diaphorase Hastophorase Hestochemistry上的鬼神经节）在NCX缺乏小鼠的肠plexus中是Foung的。（2）NCX-KO小鼠的囊泡神经节中的神经元细胞比对照组的神经节中的神经元细胞多。一氧化氮合酶（NOS）的腹膜内注射会增加阈值压力和从NCX-KO小鼠的半胱氨酸图中的剩余压力到控制水平。囊泡神经节中神经元细胞的数量增加会诱导NCX-KO小鼠中囊泡 - 尿道括约肌的功能障碍。囊泡神经细胞中一氧化氮的量对于控制囊泡 - 尿道括约肌的功能很重要。（3）在使用野生型和NCX缺陷小鼠的肠神经元cDNA的RDA方法的过程中，我们获得了新型的Kelch家族基因并命名为ND1（NCX下游基因1）。我们正在通过创建转基因和敲除小鼠来表征ND1在体内的功能。