A novel mouse model of intestinal neuronal dysplasia: visualization of the enteric nervous system

Abstract

Purpose: 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.

Methods: 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.

Results: 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.

Conclusion: 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.

Keywords: Enteric nervous system; Homozygous mutant of Ncx; Intestinal neuronal dysplasia; Sox10.