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.