Fig. 2. Inactivation of Smad4 in differentiated osteoblasts caused growth retardation and reduced bone density. (A) Smad4 mutant (Cre/Co/+ and Cre/Co/Co) and control (Co/Co) mice at 6 weeks of age showing impairment of bone growth in Smad4 mutants. (B) Soft X-ray images of femurs and tibias from 6-week-old female mice. (C) Significant loss of total bone density in Smad4 mutant mice. (D-G) Histological analysis of tibias and calvarial bone in Smad4 mutant and control mice. Sections of tibia (D,E) and lambda sagittal sutures (F,G) from 7-week-old Smad4 mutant (E,G) and control mice (D,F). ^*P<0.01. Bar, 350 µm (D,E); 180 µm (F,G).