Bone Properties of Recombinant Inbred Line - BXD Mouse

Osteoporosis is identified by reduced bone mass, decreased bone quality and altered bone micro-architecture. These traits are quantitative and also highly regulated by genetic and environmental factors. As a powerful tool for collaborative analysis of quantitative traits and gene function, BXD recombinant inbred (RI) lines mice have been used to identify genetic effects for bone density. For the first time, we investigated the bone properties of BXD RI mice by analyzing femur and tibia and compared their phenotypes of different compartments. In this study, microcomputed tomography (µCT) provided an accurate measurement on characterizing bone quality and bone architecture ex-vivo; three-point bending provided a measurement on characterizing genetic-influence based bone structural response. 51 BXD RI mouse strains were analyzed, including progenitor C57BL/6J (n=16) and DBA/2J (n=15), and two first filial generations (D2B6F1 and B6D2F1). Bones were collected from 10 to 14-week old females and males (N≥3 each group) and bone parameters were measured at three different sites by high resolution 3D micro-computed tomography: whole bone, cortical bone (mid-shaft of femur and tibia), and trabecular bone (distal femoral and proximal tibial metaphyses).Statistical analysis was performed with SAS 9.3. Differences of each compartment between BXD RI strains were first analyzed using Mixed Effects models, where each strain was considered to be independent clusters and measurements of mouse from each strain were considered to be repeated measurements. The model results were adjusted for gender and age effects. Correlations between femur and tibia were examined using graphical statistics and Spearman’s rank correlation coefficient. Strain differences were observed in bone quality and structural properties (p We conclude that a) femur-tibia association in bone morphological properties significantly vary from strain to strain, which may be caused by genetic differences among strains; b) strain-wise variations were seen in bone mass, bone morphology, bone microarchitecture along with bone structural property