Interspecific hybrids and chimeras in mice.

Interspecific hybrids and chimeras in mammals provide unique tools for investigating problems in genetics and embryology, because of the degree of disparity between the two component genotypes. We have attempted to produce hybrids and chimeras between Mus musculus, the laboratory mouse, and Mus caroli, a wild species of mouse from Southeast Asia. M. musculus and M. caroli do not normally interbreed, although sterile hybrids can be produced at a low rate by artificial insemination. Extrinsic problems of genotypic incompatibility between the fetus and the maternal environment seem to be involved in poor hybrid survival, since M. caroli blastocysts also die when transferred to the M. musculus uterus. Death is associated with the generation of maternal T-cells which are cytotoxic to M. caroli target cells in vitro. It is not yet clear whether this immune response is the primary cause of death or is secondary to breakdown of some other components of the fetal-maternal interaction. It is clear, however, that it is the trophoblast layer that mediates survival or death of the foreign embryonic cells in the M. musculus juterus, since M. caroli inner cell mass cells can survive to term after injection into M. musculus blastocysts: Viable interspecific chimeras result. Even more convincing evidence is provided by the production of viable M. caroli offspring by trophoblast vesicle reconstitution using trophoblast of M. musculus genotype and inner-cell mass of M. caroli type. Studies of properties of isolated trophoblast tissues have indicated that M. caroli trophoblast may differ from M. musculus in both its antigenic and immunosuppressive properties. Elucidation of trophoblast-uterine interactions in these various interspecific pregnancies is being aided by the development of an in situ marker system, which can distinguish cells of the two species in sectioned material by in situ hybridization with a M. musculus satellite DNA probe. This same marker is also proving a very powerful tool for analyzing cell lineage development in chimeras.