Novel exomphalos genetic mouse model: the importance of accurate phenotypic classification

J Pediatr Surg. 2013 Oct;48(10):2036-42. doi: 10.1016/j.jpedsurg.2013.04.010.

Abstract

Background: Rodent models of abdominal wall defects (AWD) may provide insight into the pathophysiology of these conditions including gut dysfunction in gastroschisis, or pulmonary hypoplasia in exomphalos. Previously, a Scribble mutant mouse model (circletail) was reported to exhibit gastroschisis. We further characterise this AWD in Scribble knockout mice.

Method: Homozygous Scrib knockout mice were obtained from heterozygote matings. Fetuses were collected at E17.5-18.5 with intact amniotic membranes. Three mutants and two control fetuses were imaged by in amnio micro-MRI. Remaining fetuses were dissected, photographed and gut length/weight measured. Ileal specimens were stained for interstitial cells of Cajal (ICC), imaged using confocal microscopy and ICC quantified.

Results: 127 fetuses were collected, 15 (12%) exhibited AWD. Microdissection revealed 3 mutants had characteristic exomphalos phenotype with membrane-covered gut/liver herniation into the umbilical cord. A further 12 exhibited extensive AWD, with eviscerated abdominal organs and thin covering membrane (intact or ruptured). Micro-MRI confirmed these phenotypes. Gut was shorter and heavier in AWD group compared to controls but morphology/number of ICC was not different.

Discussion: The Scribble knockout fetus exhibits exomphalos (intact and ruptured), in contrast to the original published phenotype of gastroschisis. Detailed dissection of fetuses is essential ensuring accurate phenotyping and result reporting.

Keywords: Abdominal wall defect; Exomphalos; Gastroschisis; In amnio micro-MRI; Interstitial cells of Cajal; Rodent model; Scrib.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Abdominal Wall / abnormalities*
  • Animals
  • Disease Models, Animal*
  • Dissection / methods
  • Gastroschisis / classification
  • Gastroschisis / genetics
  • Gastroschisis / metabolism
  • Gastroschisis / pathology*
  • Genetic Markers
  • Hernia, Umbilical / classification
  • Hernia, Umbilical / genetics
  • Hernia, Umbilical / metabolism
  • Hernia, Umbilical / pathology*
  • Interstitial Cells of Cajal / pathology
  • Intracellular Signaling Peptides and Proteins / deficiency*
  • Intracellular Signaling Peptides and Proteins / genetics
  • Magnetic Resonance Imaging / methods
  • Mice
  • Mice, Knockout
  • Phenotype*

Substances

  • Genetic Markers
  • Intracellular Signaling Peptides and Proteins
  • scribble protein, mouse