Roles of Rac1 during limb development

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To investigate the physiological functions of Rac1, a member of the small Rho GTPase family, we generated Rac1 conditional knockout mice (Rac1 cKO mice) which are characterized by limb bud mesenchyme-specific inactivation of Rac1. Rac1 cKO mice had shorter body length and lower body weight as compared with control mice. Rac1 cKO mice also showed incomplete fusion of the sternum and cranium. The most striking feature of the Rac1 cKO mice fore- and hindlimbs was profound soft tissue syndactyly because of a complete absence of interdigital programmed cell death. Furthermore, the lack of interdigital programmed cell death and associated syndactyly was related to down-regulated gene expression of BMP-2 and BMP-7, which are known to promote apoptosis in the interdigital mesenchyme.