Lead scientist Ellen Heber-Katz at the Wistar Institute first noticed that mice lacking a functional p21 gene had increased healing abilities over ten years ago. In 1996, she and her team were working with a particular type of mouse called MRL. They had pierced the mice’s ears for ID markers, but the holes closed up and healed completely. I too have pierced ears, and even though I sometimes do not wear earrings for months at a time, my holes have never healed. Not only did the mice heal holes in their ears, but they were also able to regrow cartilage and skin with no scarring. Rather than forming a scar at the wound site, the MRL mice formed a blastema, a structure normally seen only in developing embryos or in regenerative species such as salamanders.
What was up with these mice? It turned out that the MRL mice did not have active p21. When researchers examined other strains of mice that had had their p21 genes specifically knocked out, they saw the same results.
P21 is cell cycle regulator. In conjunction with other factors, it controls cell division. Under normal conditions, it is turned on in cells after DNA damage, preventing those cells from possibly running amok and becoming cancerous. Although the researchers did not see increased cancer in the MRL mice, they did notice an increase in apoptosis (programmed cell death), another cellular mechanism for removing damaged cells.To be clear, the MRL mice were not regrowing limbs. Also, the researchers did not take normal adult mice and knock out their p21 genes, the mice were born without p21. On the other hand, humans too have p21 genes (though in our case they’re called CDKN1A). Perhaps we will one day be able to selectively knock out p21 at wound sites, and then, who knows?