MODULATION OF PREIMPLANTATION EMBRYONIC-DEVELOPMENT BY ANTISENSE OLIGONUCLEOTIDES TO MAJOR HISTOCOMPATIBILITY COMPLEX GENES

The Ped (preimplantation embryo development) gene, which controls the rate of mouse preimplantation embryonic cleavage division and subseque nt survival of the embryo, maps to the Q region of the MHC (major hist ocompatibility complex). Mouse embryos were treated with antisense oli gonucleotides to mRNA for the Q region genes Q7/Q9, each of which enco des the Qa-2 antigen. The reverse transcription polymerase chain react ion (RT-PCR) was used to show that antisense treatment, but not sense treatment, decreased the level of mRNA for Qa-2 antigen in preimplanta tion embryos. Furthermore, both the expression of Qa-2 protein and the rate of embryonic cleavage division were decreased by treatment with antisense but not sense oligonucleotides. These results provide direct evidence that the Ped gene phenotype is at least partially encoded by the Q7/Q9 genes. It is likely that the mouse Ped gene has a human hom olog, perhaps within HLA-F. Identification of genes-such as the Ped ge ne-that affect survival of the embryo may be vitally important for the enhancement of animal and human reproductive success.