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Mice were generated with targeted disruptions in Hoxa7 and Hoxb7 , respectively. Mice carrying the Hoxa7 mutation are healthy. No abnormalities in the formation of the skeleton or other tissues were found in these mutants. Twelve percent of Hoxb7 −/− mutants show first and second rib defects similar to those observed in mice homozygous for a Hoxb9 mutation (Chen, F., Capecchi, M.R., 1997. Dev. Biol. 181, 186–196). Hoxb7 −/− mice are also fertile and were used to generate double mutants with Hoxa7 to reveal potential interactions between these two paralogous genes. Mice homozygous for both mutations have first and second rib defects with higher penetrance and increased expressivity, indicating a functional role for Hoxa7 in the patterning of the upper thoracic region. Although Hoxb6 , Hoxa7 , Hoxb7 , and Hoxb9 have distinctive anterior expression limits in axial mesoderm, the disruptions of these genes all yield first and second rib defects. A hypothesis is suggested to explain the observation that axial defects in these and other mouse Hox mutants appear to concentrate along the axial column at zones of transition between vertebral types.