Fig. 7. Activated HIF1 pathway causes ER stress in chondrocytes. In situ hybridization for BiP mRNA in mouse E16 proximal tibial (A,B) and P5 proximal humeral (C,D) growth plates. Note the ectopic activation of BiP mRNA around the neoplastic core of mutant growth plates (D, arrowhead). (E) BiP protein expression in control and mutant primary chondrocytes cultured under normoxic or hypoxic conditions for 1 or 5 days as revealed by western blot analysis. (F) Control and mutant chondrocytes were treated with increasing concentrations of DMOG for 2 days and then analyzed by western blot with antibodies against HIF1 and BiP. (G) Control and mutant chondrocytes were treated with 1 mM DMOG for increasing times and then analyzed by western blot with antibodies against HIF1 and BiP. Scale bar: 200 µm in A,B; 470 µm in C,D.