It is known that in Drosophila, Polycomb group (Pc-G) genes are necessary to repress expression of the homeobox genes during the anteroposterior axis patterning. Pc-G gene products make a protein complex, and synergism of the each protein among the complex influences the body patterning strongly. In mammal, the mouse homologue of the Drosophila Pc-G genes have been identified. Recent studies provide the evidence indicating that the mouse homologue of Pc-G gene products are associated in nucleus, and that these mutant mice of the Pc-G gene show homeotic transformation of the axial skeleton as observed in Drosophila Pc-G gene mutants. In order to investigate the functional correlation among mammalian Pc-G genes and the influence of the synergism among the protein complex in vivo, we have generated doubl mutants of the M33 and mel-18 gene. (1) The mutant mice of M33 +/-mel-18-/-, M33-/-mel-18 + /- gene became dead within 3 weeks after birth, but the emphasis of the genetic interaction was not recognized in skeletal abnormalities. (2) The doubl mutants of the M33 and mel-18 gene died in the early stage of embryogenesis. These findings suggest synergism among mammalian Pc-G gene products might play a crucial role not only in regulation of the homeobox gene expression during the anteroposterior axis patterning, but also in survival of individuals.