Department of Pediatric General and Urogenital Surgery, Juntendo University Graduate School of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo, 113-8421, Japan.
Division of General and Thoracic Surgery, The Hospital for Sick Children, Toronto, Canada.
Pediatr Surg Int. 2023 Nov 20;39(1):298. doi: 10.1007/s00383-023-05585-w.
Intestinal neuronal dysplasia (IND) is a congenital anomaly affecting gastrointestinal neural innervation, but the pathogenesis remains unclear. The homozygous Ncx/Hox11L.1 knockout (Ncx) mice exhibit megacolon and enteric ganglia anomalies, resembling IND phenotypes. Sox10-Venus transgenic mouse were used to visualize enteric neural crest cells in real time. This study aims to establish a novel mouse model of Sox10-Venus/Ncx mouse to study the pathogenesis of IND.
Sox10-Venus/Ncx (Ncx) (n = 8) mice and Sox10-Venus/Ncx controls (control) (n = 8) were euthanized at 4-5 weeks old, and excised intestines were examined with fluorescence microscopy. Immunohistochemistry was performed on tissue sections with neural marker Tuj1.
Ncx mice exhibited dilated cecum and small intestine. Body weight of Ncx mice was lower with higher ratio of small intestine length relative to body weight. The neural network (Sox10-Venus) was observed along the intestine wall in Ncx and control mice without staining. Ectopic and increased expression of Tuj1 was observed in both small intestine and proximal colon of Ncx mice.
This study has established a reliable animal model that exhibits characteristics similar to patients with IND. This novel mouse model can allow the easy visualization of ENS in a time- and cost-effective way to study the pathogenesis of IND.
肠神经元发育不良（IND）是一种影响胃肠道神经支配的先天性异常，但发病机制尚不清楚。Ncx/Hox11L.1 纯合敲除（Ncx）小鼠表现出巨结肠和肠神经节异常，类似于 IND 表型。Sox10-Venus 转基因小鼠用于实时可视化肠神经嵴细胞。本研究旨在建立一种新型 Sox10-Venus/Ncx 小鼠模型，以研究 IND 的发病机制。
4-5 周龄时处死 Sox10-Venus/Ncx（Ncx）（n=8）小鼠和 Sox10-Venus/Ncx 对照（对照）（n=8），并通过荧光显微镜检查离体肠道。用神经标志物 Tuj1 对组织切片进行免疫组织化学染色。
Ncx 小鼠表现出扩张的盲肠和小肠。Ncx 小鼠的体重较低，小肠长度与体重的比值较高。Ncx 和对照小鼠的肠壁上观察到神经网络（Sox10-Venus），但未染色。Ncx 小鼠的小肠和近端结肠中均观察到 Tuj1 的异位和过度表达。
本研究建立了一种可靠的动物模型，该模型表现出与 IND 患者相似的特征。这种新型小鼠模型可以以经济有效的方式方便地观察 ENS，从而研究 IND 的发病机制。
