Chimeric mice are one of the most important tools in biological research. By studying composite animals with tissues from distinct genetic lineages, scientists have gained important insights into the molecular mechanisms of disease. This powerful biomedical research tool has largely been restricted to rodents and farm animals that are distantly related from humans, and, thus, might not best approximate human disease. Now, however, rhesus monkeys have joined the chimera club—an advance that researchers hope will help bridge the gap between mice and humans.
“It is not enough to jump from mouse right to human in transplanting tissues,” says Shoukhrat Mitalipov, a developmental biologist at the Oregon National Primate Research Center in Beaverton who led the study. “We need primate models to know if tissues are truly functional.”
In their study, Mitalipov and his colleagues plucked cells from early-stage monkey embryos containing only four cells each. They then mixed the cells together into aggregates containing cells from between three and six different embryos. After growing the cells up to the blastocyst stage, they implanted 14 of the cell clusters into five females. The scientists terminated three of the pregnancies for genetic analysis, but the other two monkeys gave birth to healthy baby boys: a pair of twins named Roku and Hex (pictured here), and a singleton name Chimero. These monkeys were indeed chimeric—with some cells originating from female embryos, too—as the researchers detected multiple genotypes in the animals’ blood cells. The findings were published today in Cell.
This method stands is in stark contrast to that typically used to create chimeric rodents. In mice and rats, scientists usually inject cultured embryonic stem cells into developing embryos from another animal strain. Although Mitalipov has cloned monkey embryos in the past, and even derived embryonic stem cells, his attempts to create chimeric monkey fetuses using cultured embryonic stem cells failed repeatedly because the stem cells didn’t incorporate properly into the host embryo.
Rhesus monkeys are currently used for a host of different biomedical applications, including studies of HIV and influenza viruses. For such studies, especially those on drug therapies, which often now go directly from mouse to human testing, the addition of a chimeric monkey model will be a crucial bridge for vetting the potential translation of findings to humans.
Image courtesy of Oregon Health & Science University