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

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

Research output: Contribution to journalArticle

46 Citations (Scopus)

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 1 2009
Externally publishedYes

Fingerprint

Knockout Mice
Phenotype
Intestinal Fistula
Congenital, Hereditary, and Neonatal Diseases and Abnormalities
Urinary Tract
Rectum
In Situ Hybridization
Histology
Colon
Embryonic Structures
Anorectal Malformations
Mutation

Keywords

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

ASJC Scopus subject areas

  • Surgery

Cite this

Tai, C. C., Sala, F. G., Ford, H., Wang, K. S., Li, C., Minoo, P., ... 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

Wnt5a Knock-out Mouse as a New Model of Anorectal Malformation1 . / Tai, Cindy C.; Sala, Frederic G.; Ford, Henri; Wang, Kasper S.; Li, Changgong; Minoo, Parviz; Grikscheit, Tracy C.; Bellusci, Saverio.

In: Journal of Surgical Research, Vol. 156, No. 2, 01.10.2009, p. 278-282.

Research output: Contribution to journalArticle

Tai, CC, Sala, FG, Ford, H, Wang, KS, Li, C, Minoo, P, Grikscheit, TC & Bellusci, S 2009, 'Wnt5a Knock-out Mouse as a New Model of Anorectal Malformation1 ', Journal of Surgical Research, vol. 156, no. 2, pp. 278-282. https://doi.org/10.1016/j.jss.2009.03.087
Tai, Cindy C. ; Sala, Frederic G. ; Ford, Henri ; Wang, Kasper S. ; Li, Changgong ; Minoo, Parviz ; Grikscheit, Tracy C. ; Bellusci, Saverio. / Wnt5a Knock-out Mouse as a New Model of Anorectal Malformation1 . In: Journal of Surgical Research. 2009 ; Vol. 156, No. 2. pp. 278-282.
@article{bf70335040344b3f8402ae19bd658920,
title = "Wnt5a Knock-out Mouse as a New Model of Anorectal Malformation1",
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.",
keywords = "anorectal malformation, fistula, gastrointestinal development, imperforate anus, Wnt signaling, Wnt5a",
author = "Tai, {Cindy C.} and Sala, {Frederic G.} and Henri Ford and Wang, {Kasper S.} and Changgong Li and Parviz Minoo and Grikscheit, {Tracy C.} and Saverio Bellusci",
year = "2009",
month = "10",
day = "1",
doi = "10.1016/j.jss.2009.03.087",
language = "English (US)",
volume = "156",
pages = "278--282",
journal = "Journal of Surgical Research",
issn = "0022-4804",
publisher = "Academic Press Inc.",
number = "2",

}

TY - JOUR

T1 - Wnt5a Knock-out Mouse as a New Model of Anorectal Malformation1

AU - Tai, Cindy C.

AU - Sala, Frederic G.

AU - Ford, Henri

AU - Wang, Kasper S.

AU - Li, Changgong

AU - Minoo, Parviz

AU - Grikscheit, Tracy C.

AU - Bellusci, Saverio

PY - 2009/10/1

Y1 - 2009/10/1

N2 - 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.

AB - 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.

KW - anorectal malformation

KW - fistula

KW - gastrointestinal development

KW - imperforate anus

KW - Wnt signaling

KW - Wnt5a

UR - http://www.scopus.com/inward/record.url?scp=70249088658&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=70249088658&partnerID=8YFLogxK

U2 - 10.1016/j.jss.2009.03.087

DO - 10.1016/j.jss.2009.03.087

M3 - Article

VL - 156

SP - 278

EP - 282

JO - Journal of Surgical Research

JF - Journal of Surgical Research

SN - 0022-4804

IS - 2

ER -