Attempts to obtain fully xenogeneic fetuses in rat↔mouse model

The full-term development of the xenogeneic embryo in the uterus of the mother of differentspecies is very restricted and can occur only in certain groups of closely related mammals. Inthe case of mouse↔rat chimeras, the interspecific uterine barrier is less hostile to interspecificchimeric fetuses. In current work, we tested the development of mouse and rat fetuses in uteriof females of the opposite species. We created chimeric mouse↔rat blastocysts by injectionof mouse embryonic stem cells (ESCs) into eight-cell rat embryos and rat ESCs into eight-cellmouse embryos. Chimeras were transferred to the foster mothers of the opposite species. Despitea huge number of transferred embryos (>1000 in total for both variants), only one live fetusderived solely from the mouse ESCs was isolated at E13.5 from the rat uterus. All other fetuses andnewborns were chimeric or were built only from the cells of the recipient embryo. We examinedthe possible reason for such an outcome and found that the xenogeneic fetuses are eliminated atthe perigastrulation stage of development. Thus, we conclude that in the rat↔mouse combinationeven when extraembryonic tissues of the chimeric embryo are composed solely of the cells of thesame species as the female to which embryos are transferred, the full-term development of thepure xenogeneic fetus is very unlikely.