title: Mouse models orthologous to FGFR3-related skeletal dysplasias.
abstract: Fibroblast growth factor receptor 3 (FGFR3) is one of the membrane bound tyrosine kinases that mediate the actions of fibroblast growth factor (FGF) family members. Missense mutations in the coding regions of FGFR3 have been identified in allelic forms of short-limbed dwarfism. Using gene targeting, we demonstrated that Fgfr3 plays an essential role in endochondral ossification and that a loss-of-function mutation causes accelerated and prolonged long bone growth. Using a number of molecular genetic approaches, we also have introduced into the mouse genome a series of mutations that correspond to the missense mutations identified in individuals with achondroplasia and thanatophoric dysplasia. These mouse models mimic the human condition and can be used for further studies to identify and characterize in vivo changes associated with various Fgfr3 mutations. In addition, these models may be beneficial in future studies to attempt novel treatment strategies for short-limbed dwarfism.
authors.affiliation: Genetics of Development and Disease Branch, NIDDK, NIH, 10/9N105, 10 Center Drive, Bethesda, MD 20892, USA. Stevenb@intra.niddk.nih.gov
authors.forename: Steven G
authors.initials: SG
authors.lastname: Brodie
authors.forename: Chu-Xia
authors.initials: CX
authors.lastname: Deng
mesh_terms: D000818:Animals; D001848:Bone Diseases, Developmental / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D001842:Bone and Bones / Q000378:metabolism / Q000473:pathology; D005786:Gene Expression Regulation; D051379:Mice; D008817:Mice, Mutant Strains; D023421:Models, Animal; D008967:Molecular Biology; D020125:Mutation, Missense; D011505:Protein-Tyrosine Kinases; D051498:Receptor, Fibroblast Growth Factor, Type 3; D017468:Receptors, Fibroblast Growth Factor / Q000235:genetics* / Q000378:metabolism
chemical_list: D017468:Receptors, Fibroblast Growth Factor; C496366:Fgfr3 protein, mouse; D011505:Protein-Tyrosine Kinases; D051498:Receptor, Fibroblast Growth Factor, Type 3