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

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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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Data availability

The datasets generated and analyzed during the current study are available from the corresponding author on reasonable request.

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Acknowledgements

We thank Mr. Fumio Kanai for support for the animals in the Laboratory of Genome Research, Research Institute for Diseases of Old Age, Juntendo University Graduate School of Medicine and Ms. Mirei Takahashi for assistance in the experiments.

Funding

This work was supported by JSPS KAKENHI Grant Number (22K08721).

Author information

Authors and Affiliations

  1. Department of Pediatric General and Urogenital Surgery, Juntendo University Graduate School of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo, 113-8421, Japan

    Naho Fujiwara, Nana Nakazawa-Tanaka & Atsuyuki Yamataka

  2. Division of General and Thoracic Surgery, The Hospital for Sick Children, Toronto, Canada

    Naho Fujiwara, Dorothy Lee & Agostino Pierro

  3. Laboratory of Morphology and Image Analysis, Biomedical Research Core Facilities, Juntendo University School of Medicine, Tokyo, Japan

    Katsumi Miyahara

  4. Intractable Disease Research Center, Juntendo University School of Medicine, Bunkyo-ku, Tokyo, Japan

    Chihiro Akazawa

  5. Department Biomedical Science, Chiba University Graduate School of Medicine, Chiba, Japan

    Masahiko Hatano

Authors
  1. Naho Fujiwara
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  2. Katsumi Miyahara
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Contributions

NF performed animal experiments and the analysis of the experimental results, also wrote the whole manuscript. KM performed some of the animal experiments. NN-T and DL supervised some of the animal experiments. AP, AY, CA and MH provided advice and supervision. All the authors reviewed and approved the final manuscript.

Corresponding author

Correspondence to Naho Fujiwara.

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Fujiwara, N., Miyahara, K., Lee, D. et al. A novel mouse model of intestinal neuronal dysplasia: visualization of the enteric nervous system. Pediatr Surg Int 39, 298 (2023). https://doi.org/10.1007/s00383-023-05585-w

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