Figure 1. The Spdh allele acts as a loss and gain of function.

(A) Skeletal preparations of WT and Spdh/Spdh mice at birth (P0) and 1 week of age (P7). Spdh/Spdh mice exhibited multiple additional incompletely formed digits, fused joints, and a severe delay in ossification. Cartilage was stained with Alcian blue, bone with Alizarin red. (B) Skeletal preparations of transgenic PrxHoxd13^+21Ala mice at P0 showed a severe malformation of the radius and bending of the ulna. No major changes were seen in the digits. Introducing 1 Spdh allele (Hoxd13^+21Ala; Spdh/WT) did not change the phenotype. Mice expressing Hoxd13^+21Ala on a homozygous Spdh background (Hoxd13^+21Ala; Spdh/Spdh) showed a severe phenotype with excessive fusions and polydactyly. Mice with 1 Spdh allele and 1 inactivated Hoxd13 allele (Hoxd13^st/Spdh) showed a delay in bone formation, fusion of joints, occasional postaxial polydactyly, and a short digit 2. In addition, ectopic cartilage formation between the digits, and an uneven surface of the digit cartilage (magnification of interdigital space shown on right), was present. Original magnification, ×3.2 (left), ×4.0 (right). (C) Shh expression in E10.5 WT and Spdh embryos.