Gene expression between a congenic strain that contains a quantitative trait locus of high bone density from CAST/EiJ...

Peak bone density is an important determining factor of future osteoporosis risk. We previously identified a quantitative trait locus (QTL) that contributes significantly to high bone density on mouse chromosome 1 from a cross between C57BL/6J (B6) and CAST/EiJ (CAST) mouse strains. We then generated a congenic strain, B6.CAST-1T, in which the chromosomal fragment containing this QTL had been transferred from CAST to the B6 background. The congenic mice have a significantly higher bone density than the B6 mice. In this study we performed cDNA microarray analysis to evaluate the gene expression profile that might yield insights into the mechanisms controlling the high bone density by this QTL. This study led to several interesting observations. First, approximately 60% of 8,734 gene accessions on GEM I chips were expressed in the femur of B6 mice. The expression and function of two-thirds of these expressed genes and ESTs have not been documented previously. Second, expression levels of genes related to bone formation were lower in congenic than in B6 mice. These data are consistent with a low bone formation in the congenic mice, a possibility that is confirmed by reduced skeletal alkaline phosphatase activity in serum compared with B6 mice. Third, expression levels of genes that might have negative regulatory action on bone resorption were higher in congenic than in B6 mice. Together these findings suggest that the congenic mice might have a lower bone turnover rate than B6 mice and raise the possibility that the high bone density in the congenic mice could be due to reduced bone resorption rather than increased bone formation.