Background/Purpose: VACTERL syndrome is a common surgical condition affecti
ng the development of many midaxial organs. The etiology, embryology, and p
athogenesis of the VACTERL syndrome are not known. The authors report here
new mouse models of VACTERL syndrome involving the Sonic hedgehog (Shh) sig
naling pathway.
Methods: Mutant mice involving Shh signaling, the Shh transcription factors
Gli2-/- and Gli3-/-, Gli2-/-;Gli3+/- double heterozygotes, and Shh-/- were
analyzed.
Results: In addition to reported vertebral, anal, tracheoesophageal, and li
mb anomalies, mutant mice display cardiac, renal, and associated anomalies,
namely congenital diaphragmatic hernia and omphalocele, known to be associ
ated in VACTERL syndrome. The Shh transcription factors Gli2 and Gli3 have
specific and overlapping roles in the induction of VACTERL phenotypes in a
gene-dose-dependent manner in these mutants.
Conclusion: To the authors' knowledge, these mutant mice represent the firs
t animal model that mimics the human VACTERL syndrome, and suggests that ab
errations in Shh signaling might be involved in the VACTERL syndrome. Copyr
ight (C) 2001 by W.B. Saunders Company.