Physical and Mechanical Characteristics of Tibias from Transgenic Mice Expressing Mutant Bovine Growth Hormone Genes

Physical and mechanical characteristics of tibia from mice expressing either the M4, M11, or G119K mutant bovine growth hormone (bGH) gene and displaying large, near-normal, or small-size Phenotypes, respectively, were compared to those of non-transgenic, control mice (NTC). Three animals of each strain were euthanized at 28, 38, 48, 58, and 68 days of age. Variables were regressed against age to establish the pattern of change throughout the experiment, and the regression results are presented. Tibias from G119K were shorter (13.1 mm) and lighter (37.3 mg) than those from other strains, and M4 tibias were heavier (87.9 mg) and longer (16.6 mm) at 70 days of age. The ratio of tibia length to body weight suggests longitudinal bone growth was not reduced as much as overall growth in G119K mice. The external and internal dimensions of the G119K tibias were smaller than the other strains whereas the M4 tibias were somewhat larger. Differences in physical dimensions between the NTC and M11 mice did not greatly affect bone mechanical characteristics. Tibias from M4 mice resisted more load at both flexure and breaking compared to the other strains. At 50 days of age, stress at flexure was greater at all ages for G119K mice (12.4 kg/mm2) and was decreased in M4 mice (8.5 kg/mm2). The bGH mutations produce different effects on bone growth and its mechanical characteristics. There also may be differential tissue responsiveness to the mutant bGH analogs, as longitudinal growth was not as affected as empty body growth in the G119K mice. These transgenic mouse strains provide valuable models to study bone growth, formation, and reformation in response to GH regulation, and more importantly, the M4 and G119K mice may serve as a model in which the priorities for GH action on bone vs muscle may be determined.