Successful rescue of microsurgically produced homozygous uniparental mouse embryos via production of aggregation chimeras.

Homozygous uniparental mouse embryos, produced by microsurgical removal of the male pronucleus from fertilized eggs and diploidization of the female pronucleus with cytochalasin, were surrounded with blastomeres from normal embryos to produce chimeric embryos. A few of these chimeras developed into viable adults, and one female has reproduced using her homozygous uniparental cells as a source of gametes. The production and use of such chimeras in breeding programs could greatly shorten the period required for producing inbred strains of mammals. The data presented demonstrate that a homozygous uniparental mammalian genome, although not lethal to all cells, is extremely deleterious to normal embryonic development. Moreover, the results support the conclusion that the genome is imprinted differently in males and females during gametogenesis so that at fertilization the genomes are not functionally equivalent, and both are required for normal development.