Gross morphology and radiographic assessment of hands and feet in SHP2 cKO mice. (A) Tamoxifen was administered to control and SHP2 cKO mice 4 weeks after birth. Multiple nodules in the hands were detected within 2 to 3 weeks in the SHP2 cKO mice, which progressed and became larger over time. Shown are nodules on the hands of SHP2 cKO mice at 12 weeks of age (arrows). (B) Images are of hands of the same mice in (A) after skin removal. The nodules in the SHP2 cKO mice were attached to the bony tissue of the hands. (C) Images were taken after the skin was removed from the feet. The nodules in the SHP2 cKO mice were attached to the bony tissue of the feet. (D) Nodules in the hands of the SHP2 cKO mice at 12 weeks of age were assessed by X-ray. X-ray images showed multiple extra bony masses adjacent to the metacarpal-phalangeal and proximal interphalangeal joints with a similar intensity to the native digits. Some digit bones (ie, metacarpals, phalanges) were deformed around the nodules. Different degrees of progression were observed in SHP2 cKO mice from mild (middle panel) to severe (right panel). (E) Nodules in the feet of the SHP2 cKO mice at 12 weeks of age were assessed by X-ray. X-ray images showed an extra bony mass (white arrows) adjacent to the metatarsal-phalangeal joints and distal phalangeal bones with similar intensity to the digits (ie, metatarsals, phalanges).