We generated mice lacking Mek1 and Mek2 in osteoprogenitors (Mek1OsxMek2−/−) by crossing mice with a conditional deletion of Mek1 in osteoprogenitors (Mek1Osx) and mice with a germline deletion of Mek2 (Mek2−/−), demonstrating that inactivation of ERK in osteoprogenitors results in severe bone loss in both axial and appendicular bones along with characteristic CCD phenotypes. This evidence concerns the gene MAP2K1 and cleidocranial dysplasia 1.