Comparison of skeletal morphology of Brd2 heterozygous mice against wild type C57/B6J mice

Abstract

Objectives: The purpose of the study was to characterize age related bone lose in male and female mice lacking one functional copy of the Brd2 gene. These mice will develop age related obesity but will not develop Type II diabetes that is normally associated with obesity. Thus age and sex related changes in the skeletal morphology and structure can be assessed in response to obesity but not be confounded by the development of insulin resistance that is known to effect bone mass. Methods: Wild type and Brd2 heterozygote male and female mice were allowed to age under normal conditions in which they were fed ad libitum. Skeletal morphology and structure was assessed via µCT of the proximal metaphysis for the trabecular architecture and for the mid-diaphyseal region to assess cortical. Results: Genotype was found to play a significant role in affecting trabecular architecture in females for BV/TV, connective density, trabecular number, thickness and separation and in males for degree of anisotropy. An age-bygenotype was found to play a significant role in affecting cortical architecture in males for cortical area, total area, cortical area/total area, and medullary area. Conclusion: Brd2 heterozygote mice have significantly altered structural parameters from that of their wild type counterparts. These differences in how genotype affected the sexes suggests that the Brd2 protein is affected by sex dependent mechanism related to general metabolism and adiposity independent of insulin function.