Wnt5a knock-out mouse as a new model of anorectal malformation.
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.
Tai
Cindy C
CC
Division of Pediatric Surgery, Childrens Hospital Los Angeles, Los Angeles, California 90027, USA.
Sala
Frederic G
FG
Ford
Henri R
HR
Wang
Kasper S
KS
Li
Changgong
C
Minoo
Parviz
P
Grikscheit
Tracy C
TC
Bellusci
Saverio
S
D001003:Anal Canal / Q000002:abnormalities*; D000818:Animals; D004065:Digestive System Abnormalities / Q000235:genetics*; D004195:Disease Models, Animal; D051379:Mice; D018345:Mice, Knockout; D012007:Rectum / Q000002:abnormalities*; D051153:Wnt Proteins / Q000235:genetics*; D000071818:Wnt-5a Protein
D051153:Wnt Proteins; D000071818:Wnt-5a Protein; C438615:Wnt5a protein, mouse