To investigate the role of the T-box gene Tbx3 in the human developmental disorder ulnar-mammary syndrome (UMS), which is caused by spontaneous mutations in TBX3, Virginia Papaioannou and colleagues created Tbx3-knockout mice. They report, on , that although heterozygous mutant mice have only a mild developmental phenotype – UMS is a dominant disorder – the homozygous mutants recapitulate two of the main features of the disorder: abnormal forelimb and mammary gland development. Moreover, massive cell death of the yolk sac endoderm occurs in Tbx3-null embryos at various times in midgestation. Subsequently, and possibly as a result, mutant embryos die over several days, with none surviving to birth. These mutant mice therefore reveal a novel role for Tbx3 in the yolk sac and provide a means for investigating the role of this gene in limb and mammary gland development.
