Fibroblast growth factor receptor 2 IIIb invalidation--a potential cause of familial duodenal atresia.
OBJECTIVE
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 2IIIb (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 I, 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.
Fairbanks
Timothy J
TJ
Developmental Biology Program, Division of Pediatric Surgery, Childrens Hospital Los Angeles, Los Angeles, CA 90027, USA.
Kanard
Robert
R
Del Moral
Pierre M
PM
Sala
Frederic G
FG
De Langhe
Stijn
S
Warburton
David
D
Anderson
Kathryn D
KD
Bellusci
Saverio
S
Burns
R Cartland
RC
D000818:Animals; D004195:Disease Models, Animal; D004380:Duodenal Obstruction / Q000151:congenital* / Q000196:embryology / Q000235:genetics; D004386:Duodenum / Q000196:embryology; D005865:Gestational Age; D007409:Intestinal Atresia / Q000196:embryology / Q000235:genetics*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D051497:Receptor, Fibroblast Growth Factor, Type 2; D017468:Receptors, Fibroblast Growth Factor / Q000172:deficiency / Q000235:genetics / Q000502:physiology*
D017468:Receptors, Fibroblast Growth Factor; D051497:Receptor, Fibroblast Growth Factor, Type 2