Muenke syndrome, defined by heterozygosity for a Pro250Arg substitution in 
fibroblast growth factor receptor 3 (FGFR3), is the most common genetic cause of 
craniosynostosis in humans. We have used gene targeting to introduce the Muenke 
syndrome mutation (equivalent to P244R) into the murine Fgfr3 gene. A rounded 
skull and shortened snout (often skewed) with dental malocclusion was observed 
in a minority of heterozygotes and many homozygotes. Development of this 
incompletely penetrant skull phenotype was dependent on genetic background and 
sex, with males more often affected. However, these cranial abnormalities were 
rarely attributable to craniosynostosis, which was only present in 2/364 
mutants; more commonly, we found fusion of the premaxillary and/or zygomatic 
sutures. We also found decreased cortical thickness and bone mineral densities 
in long bones. We conclude that although both cranial and long bone development 
is variably affected by the murine Fgfr3(P244R) mutation, coronal 
craniosynostosis is not reliably reproduced.