Axial skeletal patterning in mice lacking all paralogous group 8 Hox genes

We present a detailed study of the genetic basis of mesodermal axial patter ning by paralogous group 8 Hox genes in the mouse. The phenotype of Hoxd8 l oss-of-function mutants is presented, and compared with that of Hoxb8- and Hoxc8-null mice, Our analysis of single mutants reveals common features for the Hoxc8 and Hoxd8 genes in patterning lower thoracic and lumbar vertebra e. In the Hoxb8 mutant, more anterior axial regions are affected, The three paralogous Hox genes are expressed up to similar rostral boundaries in the mesoderm, but at levels that strongly vary with the axial position. We fin d that the axial region affected in each of the single mutants mostly corre sponds to the area with the highest level of gene expression, However, anal ysis of double and triple mutants reveals that lower expression of the othe r two paralogous genes also plays a patterning role when the mainly express ed gene is defective. We therefore conclude that paralogous group 8 Hox gen es are involved in patterning quite an extensive anteroposterior (AP) axial region. Phenotypes of double and triple mutants reveal that Hoxb8, Hoxc8 a nd Hoxd8 have redundant functions at upper thoracic and sacral levels, incl uding positioning of the hindlimbs, Interestingly, loss of functional Hoxb8 alleles partially rescues the phenotype of Hoxc8- and Hoxc8/Hoxd8-null mut ants at lower thoracic and lumbar levels. This suggests that Hoxb8 affects patterning at these axial positions differently from the other paralogous g ene products. We conclude that paralogous Hox genes can have a unique role in patterning specific axial regions in addition to their redundant functio n at other AP levels.