A splicing switch and gain-of-function mutation in FgfR2-IIIc hemizygotes causes Apert/Pfeiffer-syndrome-like phenotypes

Mohammad Hajihosseini, S Wilson, L De Moerlooze, C Dickson

    Research output: Contribution to journalArticle

    131 Citations (Scopus)

    Abstract

    Intercellular signaling by fibroblast growth factors plays vital roles during embryogenesis. Mice deficient for fibroblast growth factor receptors (FgfRs) show abnormalities in early gastrulation and implantation, disruptions in epithelial-mesenchymal interactions, as well as profound defects in membranous and endochondrial bone formation. Activating FGFR mutations are the underlying cause of several craniosynostoses and dwarfism syndromes in humans. Here we show that a heterozygotic abrogation of FgfR2-exon g (IIIc) in mice causes a splicing switch, resulting in a gain-of-function mutation. The consequences are neonatal growth retardation and death, coronal synostosis, ocular proptosis, precocious sternal fusion, and abnormalities in secondary branching in several organs that undergo branching morphogenesis. This phenotype has strong parallels to some Apert's and Pfeiffer's syndrome patients.
    Original languageEnglish
    Pages (from-to)3855-3860
    Number of pages6
    JournalNational Academy of Sciences. Proceedings
    Volume98
    Issue number7
    DOIs
    Publication statusPublished - 1 Jan 2001

    Keywords

    • craniosynostosis
    • lung
    • lacrimal gland
    • sternum
    • kidney

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