ONTOGENIC LIMB BONE SCALING IN BASIC FIBROBLAST GROWTH-FACTOR (FGF-2)TRANSGENIC MICE

Basic fibroblast growth factor (FGF-2) is a potent mitogen which is re quired for normal development, particularly the development of the ske letal system, where the inhibition of FGF binding to its receptor resu lts in various skeletal malformations. The present study employed a ne wly engineered line of FGF-2 transgenic mice to determine the effects of overexpressing FGF-2 on limb bone ontogeny. We collected radiograph ic and weight data longitudinally and obtained the length, proximal, d istal, and minimum diaphyseal widths of the humerus, femur, and tibia. Because growth is nonlinear with respect to time, we used the Gompert z mathematical model to obtain parameters describing rate and timing f or each individual for each measurement. Differences in the parameters due to genotype and sex were subsequently tested with ANOVA. Transgen ic animals exhibited consistently shorter limb bones which were genera lly wider at the epiphyses than those of controls. Parameters of early growth, including initial size and proportional rate of growth, appea red to be most directly responsible for significant differences in fin al size; however, exponential decay of growth was also a marginally si gnificant factor. There were no differences between the genotypes in b ody weight, indicating that the shape anomalies observed in transgenic mice were a direct result of the action of FGF-2 rather than a genera l runting phenomenon.