The classical mouse mutant postaxial hemimelia results from a mutation in the wnt 7a gene

Abstract

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 Mullerian duct-associated sterility in both sexes. We were intrigued that both the limb and the Mullerian duct px phenotypes are similar to those caused by mutations in the gene encoding the Wnt 7a signaling molecule. In this paper, we investigate the nature of the px mutation. Morphological analysis and breeding experiments demonstrate that the px phenotype indeed results from a mutation in the Wnt 7a gene. Molecular analysis demonstrates that px results from a 515-bp deletion in the Wnt 7a gene. This generates an abnormal splicing event, which ultimately produces a truncated Wnt 7a protein of half the normal size. Thus, the px mutation is predicted to be a likely null allele of the Wnt 7a gene. Our results provide another interesting example of a classical mutation that disrupts an important patterning gene in development.