Other Src mutants induce apoptosis of osteoclasts. (A) Histological analyses of src−/− mice expressing the K295M kinase-inactive mutant that were not rescued. Arrows indicate apoptotic osteoclasts. (B) Bone volume and percentage apoptotic osteoclasts in wild-type (WT), src−/−, and src−/− mice that showed rescue or did not show rescue by TRAPSrcK295M. (C) Relative levels of expression of Src251 and SrcK295M transgenes. Lysates from osteoclast cultures of Line V Src251 and Line NN SrcK295M transgenics were normalized for TRAP levels, Src-immunoprecipitated with monclonal 327, and immunoblotted with anti-avian specific Src monoclonal EC10, which only reacts with the transgenic Src (left panel), or monoclonal 327, (right panel) which reacts only with both endogenous and transgenic Src. Similar results were seen with other transgenic lines. (D) Phenotype of mutants affecting the SH3 and SH2 domains of Src251. (E) Bone histomorphometry, osteoclast numbers, and percent apoptotic osteoclasts from mutants affecting the SH3 and SH2 domains of Src251.