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. 2023 Nov 20;39(1):298.
doi: 10.1007/s00383-023-05585-w.

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

Naho Fujiwara  1   2 , Katsumi Miyahara  3 , Dorothy Lee  4 , Nana Nakazawa-Tanaka  5 , Chihiro Akazawa  6 , Masahiko Hatano  7 , Agostino Pierro  4 , Atsuyuki Yamataka  5
Affiliations

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

Naho Fujiwara et al. Pediatr Surg Int. .

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.

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Comment in

  • Letter to the Editor.
    Kapur RP. Kapur RP. Pediatr Surg Int. 2023 Dec 13;40(1):19. doi: 10.1007/s00383-023-05614-8. Pediatr Surg Int. 2023. PMID: 38086970 No abstract available.

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