Cortical bone morphology and mechanosensitivity are modulated by genetic variations

Genetic variations are a principal factor controlling bone morphology and mechanosensitivity. Genetically distinct inbred strains of mice provide an effective model to separate genetic from epigenetic factors. For example, BALE/cByJ mice not only have different morphology than C3H mice, but also lose most of their trabecular bone volume in the femur during disuse while C3H mice are comparatively unresponsive. Double-crossing these two strains, and thus generating a new population of mice with a wide range mechanosensitivity, allows the identification of the specific chromosomal regions that define the (distinct) response of the tissue to an environmental stimulus. Here, we report disuse-induced changes in femoral mid-diaphysial morphology of F2 mice population that were scanned by in-vivo muCT at baseline, upon 3wk disuse and 3wk of subsequent reambulation. Results indicate heterogeneous population was achieved for both baseline morphology and mechanosensitivity (longitudinal change during disuse and upon reambulation). Preliminary QTL maps indicate several chromosomal regions that may be responsible for the skeletal morphology.