SPECIFICATION OF AXIAL IDENTITY IN THE MOUSE - ROLE OF THE HOXA-5 (HOX1.3) GENE

Numerous lines of study have suggested that the Hox genes, encoding pu tative transcription factors, are key genes in the establishment of th e body plan of the mammalian embryo. To examine the role of Hoxa-5 (Ho x1.3) gene during development, we have used targeted mutagenesis in em bryonic stem cells to produce a strain of mice carrying a disrupted Ho xa-5 allele. The viability of homozygous mutant mice is markedly reduc ed, with 50% of the mutant animals dying at birth or shortly thereafte r. Analysis of the skeleton of Hoxa-5 mutants reveals a number of home otic transformations restricted to the cervical and thoracic regions. Of these, one of the most frequent morphological abnormalities is the posterior transformation of the seventh cervical vertebra into the lik eness of a thoracic vertebra complete with a pair of ribs. These resul ts demonstrate that the Hoxa-5 gene has an important role in the estab lishment of the skeleton during development and contributes to the pro cess whereby the axial structures are determined.