Wnt5a Knock-out Mouse as a New Model of Anorectal Malformation1

Cindy C. Tai, Frederic G. Sala, Henri R. Ford, Kasper S. Wang, Changgong Li, Parviz Minoo, Tracy C. Grikscheit, Saverio Bellusci

Research output: Contribution to journalArticle

48 Scopus citations

Abstract

Background: Anorectal malformations (ARM) represent a variety of congenital disorders that involve abnormal termination of the anorectum. Mutations in Shh signaling and Fgf10 produce a variety of ARM phenotypes. Wnt signaling has been shown to be crucial during gastrointestinal development. We therefore hypothesized that Wnt5a may play a role in anorectal development. Methods: Wild type (WT), Wnt5a+/- and Wnt5a-/- embryos were harvested from timed pregnant mice from E15.5 to E18.5, and analyzed for anorectal phenotype. Tissues were processed for whole-mount in situ hybridization and histology. Results: Wnt5a is expressed in the embryonic WT colon and rectum. Wnt5a-/- mutants exhibit multiple deformities including anorectal malformation. A fistula between the urinary and intestinal tracts can be identified as early as E15.5. By E18.5, the majority of the Wnt5a-/- mutants display a blind-ending pouch of the distal gut. Conclusions: The expression pattern of Wnt5a and the ARM phenotype seen in Wnt5a-/- mutants demonstrate the critical role of Wnt5a during anorectal development. This study establishes a new model of ARM involving the Wnt5a pathway.

Original languageEnglish (US)
Pages (from-to)278-282
Number of pages5
JournalJournal of Surgical Research
Volume156
Issue number2
DOIs
StatePublished - Oct 2009

Keywords

  • Wnt signaling
  • Wnt5a
  • anorectal malformation
  • fistula
  • gastrointestinal development
  • imperforate anus

ASJC Scopus subject areas

  • Surgery

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    Tai, C. C., Sala, F. G., Ford, H. R., Wang, K. S., Li, C., Minoo, P., Grikscheit, T. C., & Bellusci, S. (2009). Wnt5a Knock-out Mouse as a New Model of Anorectal Malformation1. Journal of Surgical Research, 156(2), 278-282. https://doi.org/10.1016/j.jss.2009.03.087