Functional equivalence and rescue among group 11 Hox gene products in vertebral patterning

Hoxa-11 and Hoxd-11 are paralogous genes required for proper development of the vertebral column, the limbs, and the urogenital system. To further explore the functional relationship between these genes, as well as the potential rescue of one function by the other, we have introduced a Hoxd-11-expressing transgene into Hoxa-11/Hoxd-11 mutant genetic backgrounds. A range of phenotypes was observed, with transgenic mice displaying as few as four lumbar vertebrae while double mutant mice had as many as eight. When transgenic, double homozygote mutant animals showed six lumbar vertebrae, instead of the eight usually observed. The phenotypic rescue of these genotypes shows that the Hoxa-11 and Hoxd-11 products are functionally equivalent and that extra doses of Hoxd-11 can rescue Hoxa-11 loss of function.