Fibroblast growth factor receptor 2 IIIb invalidation - A potential cause of familial duodenal atresia

Background/Purpose: Duodenal atresia (DA) occurs in 1 in every 6,000 live births and represents a significant surgically correctable cause of intestinal obstruction in the neonate. Familial or congenital DA has been reported, implying that at least some cases of DA are the result of genetic, heritable abnormalities. The genes controlling duodenal development are incompletely understood. Fibroblast growth factor receptor 211lb (Fgfr2b) is known to play a critical role in the development of multiple organ systems including other gastrointestinal tract (GIT) structures. This study shows the key role of Fgfr2b in normal duodenal development and the pathogenesis of DA. Methods: Wild type (Wt) and Fgfr2b(-/-) embryos were harvested from timed pregnant mothers at stage E18.5 and were analyzed for duodenal phenotype. Results: Inactivation of Fgfr2b results in DA. DA is present in the Fgf2b(-/-) mutants with a 35% penetrance. The duodenal phenotype of the Fgf2b(-/-) mutants ranges from normal to a mucosal web, type 1, and type III atresia. Conclusions: Fgfr2b is a critical regulatory gene in the development of the duodenum. Fgfr2b invalidation (Fgfr2b(-/-) mutant) results in a reproducible, autosomal recessive duodenal atresia phenotype with incomplete penetrance and a variable phenotype. (C) 2004 Elsevier Inc. All rights reserved.