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01.12.2023 | Original Article

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

verfasst von: Naho Fujiwara, Katsumi Miyahara, Dorothy Lee, Nana Nakazawa-Tanaka, Chihiro Akazawa, Masahiko Hatano, Agostino Pierro, Atsuyuki Yamataka

Erschienen in: Pediatric Surgery International | Ausgabe 1/2023

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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.

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Titel: A novel mouse model of intestinal neuronal dysplasia: visualization of the enteric nervous system
verfasst von: Naho Fujiwara
Katsumi Miyahara
Dorothy Lee
Nana Nakazawa-Tanaka
Chihiro Akazawa
Masahiko Hatano
Agostino Pierro
Atsuyuki Yamataka
Publikationsdatum: 01.12.2023
Verlag: Springer Berlin Heidelberg
Erschienen in: Pediatric Surgery International / Ausgabe 1/2023
Print ISSN: 0179-0358
Elektronische ISSN: 1437-9813
DOI: https://doi.org/10.1007/s00383-023-05585-w

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