The zebrafish mutant lessen: an experimental model for congenital enteric neuropathies

• Published in: Neurogastroenterology and motility 2016-03, Vol.28 (3), p.345-357
• Main Authors: Uyttebroek, L., Shepherd, I. T., Vanden Berghe, P., Hubens, G., Timmermans, J.‐P., Van Nassauw, L.
• Format: Article
• Language: English
• Subjects: Animals; congenital enteric neuropathies; Danio rerio; Disease Models, Animal; enteric nervous system; Enteric Nervous System - physiopathology; Gastrointestinal Motility - genetics; Immunohistochemistry; Interstitial Cells of Cajal - metabolism; Interstitial Cells of Cajal - pathology; Intestinal Pseudo-Obstruction - genetics; Intestinal Pseudo-Obstruction - physiopathology; lessen; Motility; Mutation; Small intestine; Trans-Activators - genetics; Zebrafish; Zebrafish Proteins - genetics
• ISSN: 1350-1925; 1365-2982
• DOI: 10.1111/nmo.12732

Background Congenital enteric neuropathies of the distal intestine (CEN) are characterized by the partial or complete absence of enteric neurons. Over the last decade, zebrafish has emerged as a leading model organism in experimental research. Our aim was to demonstrate that the mutant zebrafish, lessen, expressing CEN characteristics, is an equally valuable animal model alongside mammalian models for CEN, by studying its enteric phenotype. Methods The effect of the lessen mutation on the development of the enteric nervous system (ENS), interstitial cells of Cajal (ICC), and intestinal motility in each intestinal region of mutant and wild‐type (wt) zebrafish embryos at 3–6 dpf, was analyzed by immunofluorescent detection of neurochemical markers and motility assays. Key Results Development of intestinal motility in the mutant was delayed and the majority of the observed contractions were disturbed. A significant disturbance in ENS development resulted in a distal intestine that was almost free of neuronal elements, in reduced neuronal density in the proximal and mid‐intestine, and in a defect in the expression of neurochemical markers. Furthermore, markedly disturbed development of ICC gave rise to a less dense network of ICC. Conclusions & Inferences The observed alterations in intestinal motility, intrinsic innervation and ICC network of the mutant in comparison with the wt zebrafish, are similar to those seen in the oligo‐ and aganglionic regions of the intestine of CEN patients. It is concluded that the zebrafish mutant lessen is an appropriate animal model to investigate CEN. This study shows that the zebrafish mutant embryo lessen, revealing alterations in intestinal motility, intrinsic innervations and ICC network, is an appropriate model to investigate congenital enteric neuropathies.