Quote from Ratbehavior.org:
"Rats and mice are not that closely related. Under normal circumstances, rats and mice are not attracted to each other and will not mate. Even if the sperm of one and the eggs of the other are mixed together artificially, fertilization will not occur: the eggs of one do not allow entry of the other's sperm.
These natural barriers can be overcome in a laboratory, at least at first. Such attempts typically result in a hybrid embryo which dies after a few cell divisions.
For example, the egg's protective covering can be stripped off, allowing the sperm of the other species access to the egg. Sperm can also be injected directly into the egg. When this is done, fertilization occurs. The resulting hybrid embryo is not viable, however. It typically goes through one cell division, resulting in a two-cell embryo, then it degenerates.
Another technique involves removing the nucleus (which contains most of the DNA) from a mouse egg and replacing it with a rat's nucleus. The resulting embryo has 100% rat nuclear DNA, enclosed in a mouse egg with mouse cell contents (cytoplasm). These nuclear transplant hybrids sometimes live to the 2-cell stage, but then they degenerate. The rat nucleus and the mouse cytoplasm are fundamentally incompatible.
Early stage embryos can also be merged, creating chimeras. Early stage embryos are just tiny clusters of a few undifferentiated cells. Chimeras are typically created by combining two early-stage embryos, producing a single merged embryo. The resulting individual is made up of two populations of cells, each descended from one of two fertilized ova. Chimeras have been attempted between species, including rats and mice. These were created by merging early stage rat and mouse embryos. The resulting chimeras developed normally in vitro, but when they were inserted into a hormonally primed host they were lost during or shortly after implantation.
In one case, however, using a different technique, a few of the chimeric rat-mouse embryos implanted successfully. They developed normally in vivo for about a week, before being removed and examined. The researchers found that the mouse cells gained the advantage: the mouse cells came to dominate the embryo and rat cells became rare.
Secondary chimeras are created when cells, organs, or tissue from one species are implanted into another. This procedure (called xenografting), is frequently and successfully performed in laboratories. For example, rat bone marrow can be injected into an immunosuppressed mouse, where it takes hold and produces white blood cells. Or a piece of rat skin could be grafted onto an immunosuppressed mouse. These mice with rat-tissue transplants have cells from both species, and therefore fit the definition of a chimera, but they are technically not hybrids.
Two additional techniques deserve mention: the creation of transgenic rats and rat-mouse hybrid cell lines.
Transgenic rats are rats that carry a gene from another species. The foreign gene is inserted into the fertilized rat egg, and the resulting rat carries the new gene in every one of its cells. Many types of transgenic animals have been produced, including rats that carry a mouse gene. The genome of these transgenic rats is almost 100% rat, of course, as they only have one or a few genes from other species.
Lastly, hybrid cell lines can be created in laboratories by fusing cells from two species and maintaining the resulting merged cells in a culture medium. Many such hybrid cell lines have been created, including rat-mouse hybrid cell lines. These cells will not, however, grow up to be a whole hybrid organism."