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TY - JOUR AU - Condie, Brian G. AU - Capecchi, Mario R. PY - 1994 DA - 1994/07/01 TI - Mice with targeted disruptions in the paralogous genes hoxa-3 and hoxd-3 reveal synergistic interactions JO - Nature SP - 304 EP - 307 VL - 370 IS - 6487 AB - THE Hox genes encode transcription factors which mediate the formation of the mammalian body plan along the anteroposterior and appendicular axes1–15. Paralogous Hox genes within the separate linkage groups are closely related with respect to DNA sequence and expression16,17, suggesting that they could have at least partially redundant functions. We showed previously that mice homozygous for independent targeted disruptions in the paralogous genes hoxa-3 and hoxd-3 had no defects in common1,8. But our current analysis of double mutants has revealed strong, dosage-dependent interactions between these genes. We report here that in hoxd-3- homozygotes the first cervical vertebra, the atlas, is homeotically transformed to the adjacent anterior structure. Unexpectedly, in double mutants, rather than observing a more extensive homeotic transformation, the entire atlas is deleted. These observations are interpreted in terms of a model in which these Hox genes differentially regulate the proliferation rates of the appropriate sets of precursor cells. SN - 1476-4687 UR - https://doi.org/10.1038/370304a0 DO - 10.1038/370304a0 ID - Condie1994 ER -