The DDK inbred strain as a model for the study of interactions between parental genomes and egg cytoplasm in mouse preimplantation development.

The DDK strain of mice has unusual genetic properties. When females of this strain are crossed to males of other strains, they generally exhibit a very low fertility, whereas reciprocal crosses are fully fertile as are the intrastrain crosses. The observed low fertility results from early embryonic lethality, the F1 embryos dying around the late morula-early blastocyst stage. Nuclear transplantation experiments between hybrid eggs of BALB/c and DDK strains has shown that failure of F1 (DDK female x BALB/c male) embryos to develop is not due to the combination per se of maternal (DDK) and paternal (BALB/c) genomes but rather to an incompatibility between paternal (BALB/c) genomic contribution and DDK cytoplasm. This incompatibility does not occur between a female BALB/c pronucleus and the DDK cytoplasm, suggesting the involvement of a differential imprinting of parental genomes. Introduction of cytoplasts isolated from DDK 1- to 8-cell embryos into BALB/c female x BALB/c male or BALB/c female x DDK male embryos of the corresponding developmental stage demonstrate that the cytoplasm of DDK embryos prevents the formation of normal blastocysts through a specific interaction with the paternal component of the BALB/c diploid nucleus. Genetic and molecular studies are underway to try and isolate the gene(s) responsible for the failure of (DDK female x BALB/c male)F1 embryos. These experiments should help in our understanding of nucleocytoplasmic interactions and the respective roles of parental genomes in early embryonic development.