Localized enteric neural deficiency and reduced nerve-mediated anorectal contractility in immunodeficient RetS812F/+ mice
Abstract
Evaluating cell-based therapies for the enteric nervous system (ENS) requires an in vivo environment with a localized enteric neural-deficient region. However, preclinical studies using human cells are limited by the lack of suitable animal models; conventional aganglionic models often suffer from early lethality, and there are few immunodeficient strains with a defined enteric neural-deficient segment for xenotransplantation. In this study, we established the B6RGS- Ret S812F/+ mouse, a novel immunodeficient strain with a localized deficiency of enteric nerves and reduced nerve-related anorectal contraction. While these mice did not exhibit overt defecation defects or stool congestion, this phenotype allowed for the survival period necessary to perform transplantation experiments. Using the B6RGS background, we observed the short-term retention of human induced pluripotent stem cell-derived vagal neural crest cells within the distal anorectum. Our results suggest that the B6RGS- Ret S812F/+ mouse may serve as a practical recipient for evaluating the initial engraftment of human-derived cell therapies for enteric nerve deficiencies.
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BibTeX
@article{komoike2026localized,
title = {{Localized enteric neural deficiency and reduced nerve-mediated anorectal contractility in immunodeficient RetS812F/+ mice}},
author = {Yusaku Komoike and Teruyoshi Yamashita and Taiki Nakajima and Motohito Goto and Masafumi Yamamoto and Mukhamad Sunardi and Hirokazu Matsumoto and Hideki Enomoto and Makoto Ikeya},
journal = {Scientific Reports},
year = {2026},
month = oct,
doi = {10.1038/s41598-026-75879-1},
url = {https://www.nature.com/articles/s41598-026-75879-1},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Localized enteric neural deficiency and reduced nerve-mediated anorectal contractility in immunodeficient RetS812F/+ mice
AU - Yusaku Komoike
AU - Teruyoshi Yamashita
AU - Taiki Nakajima
AU - Motohito Goto
AU - Masafumi Yamamoto
AU - Mukhamad Sunardi
AU - Hirokazu Matsumoto
AU - Hideki Enomoto
AU - Makoto Ikeya
PY - 2026
DA - 2026/10/16
JO - Scientific Reports
DO - 10.1038/s41598-026-75879-1
UR - https://www.nature.com/articles/s41598-026-75879-1
AB - Evaluating cell-based therapies for the enteric nervous system (ENS) requires an in vivo environment with a localized enteric neural-deficient region. However, preclinical studies using human cells are limited by the lack of suitable animal models; conventional aganglionic models often suffer from early lethality, and there are few immunodeficient strains with a defined enteric neural-deficient segment for xenotransplantation. In this study, we established the B6RGS- Ret S812F/+ mouse, a novel immunodeficient strain with a localized deficiency of enteric nerves and reduced nerve-related anorectal contraction. While these mice did not exhibit overt defecation defects or stool congestion, this phenotype allowed for the survival period necessary to perform transplantation experiments. Using the B6RGS background, we observed the short-term retention of human induced pluripotent stem cell-derived vagal neural crest cells within the distal anorectum. Our results suggest that the B6RGS- Ret S812F/+ mouse may serve as a practical recipient for evaluating the initial engraftment of human-derived cell therapies for enteric nerve deficiencies.
SN - 2045-2322
ER -