The Classical Mouse Mutant Postaxial Hemimelia Results from a Mutation in theWnt7a Gene

The study of spontaneous mutations has aided the understanding of developmental processes. A large collection of spontaneous or “classical” mouse mutations has been accumulated over many decades. One of the mutations causes the postaxial hemimelia (px) phenotype, which consists of limb patterning defects accompanied by Müllerian duct-associated sterility in both sexes. We were intrigued that both the limb and the Müllerian ductpxphenotypes are similar to those caused by mutations in the gene encoding the Wnt 7a signaling molecule. In this paper, we investigate the nature of thepxmutation. Morphological analysis and breeding experiments demonstrate that thepxphenotype indeed results from a mutation in theWnt7a gene. Molecular analysis demonstrates thatpxresults from a 515-bp deletion in theWnt7a gene. This generates an abnormal splicing event, which ultimately produces a truncated Wnt 7a protein of half the normal size. Thus, thepxmutation is predicted to be a likely null allele of theWnt7a gene. Our results provide another interesting example of a classical mutation that disrupts an important patterning gene in development.