title: The zebrafish mutant lessen: an experimental model for congenital enteric neuropathies.
abstract: 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.
  
  
  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
  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.
authors.affiliation: Laboratory of Human Anatomy and Embryology, Faculty of Medicine and Health Sciences, University of Antwerp, Antwerpen, Belgium.
authors.forename: L
authors.initials: L
authors.lastname: Uyttebroek
authors.affiliation: Department of Biology, Emory University, Atlanta, GA, USA.
authors.forename: I T
authors.initials: IT
authors.lastname: Shepherd
authors.affiliation: Laboratory for Enteric NeuroScience (LENS), Translational Research in GastroIntestinal Disorders (TARGID), Department of Clinical and Experimental Medicine, University of Leuven, Leuven, Belgium.
authors.forename: P
authors.initials: P
authors.lastname: Vanden Berghe
authors.affiliation: Laboratory of Human Anatomy and Embryology, Faculty of Medicine and Health Sciences, University of Antwerp, Antwerpen, Belgium.
authors.forename: G
authors.initials: G
authors.lastname: Hubens
authors.affiliation: Laboratory of Cell Biology and Histology, Department of Veterinary Sciences, University of Antwerp, Antwerpen, Belgium.
authors.forename: J-P
authors.initials: JP
authors.lastname: Timmermans
authors.affiliation: Laboratory of Human Anatomy and Embryology, Faculty of Medicine and Health Sciences, University of Antwerp, Antwerpen, Belgium.
authors.forename: L
authors.initials: L
authors.lastname: Van Nassauw
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D017615:Enteric Nervous System / Q000503:physiopathology*; D005769:Gastrointestinal Motility / Q000235:genetics*; D007150:Immunohistochemistry; D056885:Interstitial Cells of Cajal / Q000378:metabolism / Q000473:pathology; D007418:Intestinal Pseudo-Obstruction / Q000235:genetics* / Q000503:physiopathology; D009154:Mutation; D015534:Trans-Activators / Q000235:genetics*; D015027:Zebrafish; D029961:Zebrafish Proteins / Q000235:genetics*
chemical_list: C515836:Med24 protein, zebrafish; D015534:Trans-Activators; D029961:Zebrafish Proteins
keywords: congenital enteric neuropathies; enteric nervous system; lessen; motility; zebrafish