Eur J Pediatr Surg 2019; 29(04): 361-367
DOI: 10.1055/s-0039-1694745
Review Article
Georg Thieme Verlag KG Stuttgart · New York

Animal Models of Hirschsprung's Disease: State of the Art in Translating Experimental Research to the Bedside

Naho Fujiwara
1  Department of Pediatric General and Urogenital Surgery, Juntendo University Graduate School of Medicine, Bunkyo-ku, Tokyo, Japan
,
Nana Nakazawa-Tanaka
2  Department of Pediatric Surgery, Nerima Hospital, Juntendo University, Nerima-ku, Tokyo, Japan
,
Atsuyuki Yamataka
1  Department of Pediatric General and Urogenital Surgery, Juntendo University Graduate School of Medicine, Bunkyo-ku, Tokyo, Japan
› Author Affiliations
Further Information

Publication History

26 June 2019

04 July 2019

Publication Date:
20 August 2019 (online)

Abstract

Hirschsprung's disease (HSCR) is caused by incomplete colonization of enteric neural crest-derived cell (ENCC) in the bowel, the failure of ENCCs to proliferate, differentiate, and migrate leads to an absence of enteric neurons in the distal colon, resulting in colonic motility dysfunction. Various animal models of HSCR have been important in the understanding of the anatomy and pathophysiology of the disease and in the discovery of genes involved in HSCR. Four types of HSCR animal models have been developed: teratogen-induced, surgically created, naturally occurring models, and knockout models. Mutations in several genes affect enteric nervous system (ENS) development and can have pleiotropic effects on this system. Furthermore, certain animal models are informative regarding how such molecules control the development and functional differentiation of the ENS. In this article, we summarize recent advances in this field and highlight opportunities for new discoveries.