Fgfr3 Conditional Knockout mouse models

Unlike its paralogs, Fgfr3 acts predominantly as a negative regulator of endochondral bone growth, and the mouse ortholog of human FGFR3 encodes a receptor whose activation in growth plate chondrocytes suppresses proliferation and hypertrophic differentiation through STAT1 and MAPK, which is why gain of function alleles cause dwarfism rather than overgrowth. The transmembrane G380R substitution causes achondroplasia, K650E and K650M in the activation loop cause thanatophoric dysplasia type II and SADDAN, and null mice are viable with skeletal overgrowth and inner ear defects, exactly inverting the human mutant phenotype. In cancer, S249C and Y375C drive urothelial carcinoma through ligand-independent disulfide dimerization and FGFR3-TACC3 fusions drive glioma, both targets for erdafitinib class inhibitors. Allele logic is therefore unusually clean: knockin the specific human activating codon for skeletal dysplasia and inhibitor testing, and use nulls only when asking about growth restraint. Fgfr1 and Fgfr2 do not substitute for this inhibitory function, so single-locus knockins are interpretable.

Conditional deletion of Fgfr3 limits the genetic change to the lineage you choose. That helps in oncology, immunology, and metabolic work where systemic loss would muddy the read. After you confirm Cre specificity, crossing to Fgfr3 floxed stock yields usable cohorts.