SKELETAL OVERGROWTH AND DEAFNESS IN MICE LACKING FIBROBLAST GROWTH-FACTOR RECEPTOR 3

Fibroblast growth factor receptor 3 (Fgfr3) is a tyrosine kinase recep tor expressed in developing bone, cochlea, brain and spinal cord. Acho ndroplasia, the most common genetic form of dwarfism, is caused by mut ations in FGFR3. Here we show that mice homozygous for a targeted disr uption of Fgfr3 exhibit skeletal and inner ear defects. Skeletal defec ts include kyphosis, scoliosis, crooked tails and curvature and overgr owth of long bones and vertebrae. Contrasts between the skeletal pheno type and achondroplasia suggest that activation of FGFR3 causes achond roplasia. Inner ear defects include failure of pillar cell differentia tion and tunnel of Corti formation and result in profound deafness. Ou r results demonstrate that Fgfr3 is essential for normal endochondral ossification and inner ear development.