FIGURE 2.

Cre-mediated somatic loss of Pkd1 results in loss of bone mass. A, effects of Pkd1^Δflox allele on BMD at 16 weeks of age. Similar to Beier Pkd1 heterozygous mice (Pkd1^m1Bei/+), there was ∼7–9% reduction in both male and female of BMD in single excised floxed Pkd1 heterozygous mice (Oc-Cre;Pkd1^flox/+) compared with age-matched control mice (Pkd1^flox/+), and an even greater reduction (13–14%) in double heterozygous Oc-Cre;Pkd1^flox/m1Bei (Pkd1^Oc-cko) mice, indicating an additive effect of global mutant and conditional deleted Pkd1 alleles on loss of bone mass. B, age-dependent effects of Pkd1^Δflox allele on BMD. Double heterozygous Pkd1^Oc-cko mice displayed a significant decrease in femur BMD compared with Pkd1^m1Bei/+ mice until 16 weeks of age but not at 6 weeks of age, indicating an age-dependent effect of Pkd1^Δflox allele on bone mass. C, effects of Pkd1^Δflox allele on bone structure of femurs and midshaft diaphyses. μCT analysis of the distal femoral metaphyses and midshaft diaphyses revealed that double heterozygous Pkd1^Oc-cko mice had greater loss in both trabecular and cortical bone than single Oc-Cre;Pkd1^flox/+ and Pkd1^m1Bei/+ heterozygous mice, consistent with additive effects of global mutant and conditional deleted Pkd1 alleles on bone structure and a direct role of Pkd1 in bone. Data represent the mean ± S.D. from 8–10 individual mice. *, significant difference from control (Pkd1^flox/+); @, significant difference from single heterozygous Oc-Cre;Pkd1^flox/+; #, significant difference from single heterozygous Oc-Cre;Pkd1^flox/+ and Pkd1^flox/m1Bei mice at p < 0.05, respectively.