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J Surg Res. 2009 Oct;156(2):278-82. doi: 10.1016/j.jss.2009.03.087. Epub 2009 May 8.

Wnt5a knock-out mouse as a new model of anorectal malformation.

Author information

1
Division of Pediatric Surgery, Childrens Hospital Los Angeles, Los Angeles, California 90027, USA.

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.

PMID:
19577771
PMCID:
PMC3412158
DOI:
10.1016/j.jss.2009.03.087
[Indexed for MEDLINE]
Free PMC Article

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