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The missense mutation W290R in Fgfr2 causes developmental defects from aberrant IIIb and IIIc signaling
Author(s) -
Mai S.,
Wei K.,
Flenniken A.,
Adamson S. L.,
Rossant J.,
Aubin J. E.,
Gong S.G.
Publication year - 2010
Publication title -
developmental dynamics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.634
H-Index - 141
eISSN - 1097-0177
pISSN - 1058-8388
DOI - 10.1002/dvdy.22314
Subject(s) - missense mutation , biology , gene isoform , exon , mutant , alternative splicing , mutation , fibroblast growth factor , rna splicing , fibroblast growth factor receptor , microbiology and biotechnology , fibroblast growth factor receptor 2 , genetics , gene , cancer research , receptor , rna
Missense mutations in the Fibroblast Growth Factor Receptor 2 ( FGFR2 ) have been identified in human craniosynostotic syndromes such as Crouzon (CS) and Pfeiffer (PS). FGFR2 has two major isoforms, IIIb and IIIc, generated through alternative splicing with their own temporal, spatial, and ligand‐binding specificities. In this study, we report the identification and characterization of a missense mutation in codon 290 of murine Fgfr2 (W290R). The defects in W290R mutants are suggestive of disruption of signalling in both IIIb and IIIc isoforms of the Fgfr2 gene. Heterozygous mutants presented with features resembling those found in patients with CS. Fgfr2 W290R homozygotes displayed constitutive FGFR2 activation with increased, but correct tissue‐specific, expression of the IIIb and IIIc isoforms in many of the defective organs. Our Fgfr2 W290R mouse model thus represents an excellent mouse model of CS to probe the many questions around the pathogenesis of craniosynostotic birth defects consequent to defects in FGF signaling. Developmental Dynamics 239:1888–1900, 2010. © 2010 Wiley‐Liss, Inc.