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. musculusand M. carolido 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. caroliblastocysts also die when transferred to the M. musculusuterus. Death is associated with the generation of maternal T‐cells which are cytotoxic to M. carolitarget 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. musculusjuterus, since M. caroliinner cell mass cells can survive to term after injection into M. musculusblastocysts: Viable interspecific chimeras result. Even more convincing evidence is provided by the production of viable M. carolioffspring by trophoblast vesicle reconstitution using trophoblast of M. musculusgenotype and inner‐cell mass of M. carolitype. Studies of properties of isolated trophoblast tissues have indicated that M. carolitrophoblast may differ from M. musculusin 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. musculussatellite DNA probe. This same marker is also proving a very powerful tool for analyzing cell lineage development in chimeras.