Both conditional mouse models developed syndactylies as a consequence of disturbed interdigital apoptosis, which we show to be due to reduced expression of two key morphogens: sonic hedgehog (Shh) and bone morphogenic protein 2 (Bmp2).
Thus, the brachydactyly type A2 phenotype (L441P) is caused by inhibition of the ligand-receptor interaction, whereas the symphalangism phenotype (R438L) is caused by a loss of receptor-binding specificity, resulting in a gain of function by the acquisition of BMP2-like properties.