Scientists in Japan have developed a rat-mouse hybrid embryo from a single frozen rat chromosome transplanted into a mouse egg cell. The achievement is proof that genetic material can sometimes remain functional after cryopreservation and be expressed inside the cells of a completely different species. This is giving renewed hope to the idea that we may one day be able to partially resurrect extinct species and study lost traits.
The problem with cloning
One of the things preventing scientists from studying the function of genes from extinct species is that the cells are dead and the DNA is damaged. And cloning entire animals, such as woolly mammoths, has proven to be a nonstarter because it requires high-quality, intact genetic material, usually including nuclei, as well as a supply of eggs from closely related surrogate species.
But this new research, which is published in the journal Scientific Reports, bypasses the need for intact cells or whole organisms by reanimating a single chromosome.
“This study demonstrated that a single chromosome from a frozen extinct species can be functionally revived and its transcriptional activity assessed within an interspecies oocyte,” the study authors wrote in their paper.
Reanimating the DNA
The starting point was taking nuclei from the dead blood cells of a rat that had been frozen for more than a year. The team then injected them into unfertilized mouse eggs, which forced loose rat DNA to wind itself into chromosomes.
After plucking out just one, the scientists injected it into a fresh mouse egg, which was then fertilized using normal mouse sperm. The resulting embryo was grown in the lab until it became a cluster of cells known as a blastocyst.
From this early embryonic stage, the researchers harvested stem cells that all permanently carried an extra rat chromosome on top of the full mouse complement of 40 chromosomes. These hybrid stem cells were injected into normal mouse embryos, resulting in chimeric rodents with both mouse and rat DNA.
The researchers were able to check whether the rat chromosome was actively functioning because the original rat blood cells were engineered to express a green fluorescent marker protein (GFP). The resulting mice had glowing green patches in their brains, hearts, muscles and intestines. What’s more, the mouse hearts were actively expressing a rat gene called Hsp90ab1.
“Our findings demonstrate that even chromosomes retrieved from long-term frozen specimens can retain sufficient functional integrity to be maintained in pluripotent cells and support transcriptional activity in vivo,” the researchers said.
Future directions
Don’t expect to see extinct animals walking around anytime soon as a result of this research. What it has done, though, is give us a potentially viable way to study genes from species that have long since died out, provided, of course, that the material is still intact.