Many species of starfish relish oysters, clams and other shellfish, much to the chagrin of fishermen who watch over oyster beds and farms. Legend has it that oyster fishermen used to dispose of any starfish they dredged up by cutting the creatures in half and tossing them back into the ocean. Since starfish can regenerate lost limbs, the fishermen unwittingly doubled their foes' numbers. It's hard to say exactly how true this oft-repeated story is, but starfish's regenerative talents are biological fact. Salamanders, newts and many other amphibians can regrow severed limbs too, replacing all the missing bone, muscle, nerves and skin without any trace of scar tissue. By and large, mammals are not so fortunate. Perhaps the most notable exception is a particular strain of lab mouse known as Murphy Roths Large (MRL), which seals small holes in its ears and regrows toetips thanks to its unique gene expression.
Now, scientists have confirmed that at least two species of wild mice in Africa can swiftly regenerate missing skin, hair follicles, fat cells and cartilage much like salamanders and newts. The new study—coupled with research on MRL mice—suggests that tissue regeneration may not be as uncommon in mammals as once thought and that the mammalian genome conceals a latent ability to regrow damaged body parts.
In discussions with ecologists, biologist Ashley Seifert of the University of Florida learned that African spiny mice frequently lose their tails—in the same way a salamander's tail might detach in the mouth of a hungry bird—and that large chunks of the rodents' skin easily slough off their bodies, possibly as a related defense against predators. Seifert wondered, though, how any mammal could manage to lose so much skin and still survive. Surely the animal would have to grow most of that skin back.
A few months later, Seifert traveled to Kenya and began trapping spiny mice (particularly Acomys kempi and Acomys percivali) in the rocky hills where the rodents live. Every time one of the captured spiny mice struggled in his grasp, its skin peeled off. In mechanical tests, Seifert discovered that it takes nearly 77 times more energy to break typical mouse skin than to tear African spiny mouse skin. On a cellular level, typical mouse skin and African spiny mouse skin look more or less the same. However, spiny mice have far larger hair follicles than typical mice. The follicles take up so much room, Seifert and his colleagues reason, that spiny mouse skin has much less connective tissue holding it together than typical mouse skin, making it more fragile.
When Seifert and his colleagues gave the spiny mice a few nicks, bleeding promptly stopped and scabs formed rapidly. The mice grew new skin over their wounds within 3 days; adult rats take between 5 to 7 days to do the same. 10 days after injury, the spiny mice's skin had healed without much scarring. Instead of arranging new collagen fibers in the tough, dense networks typical of scars, the spiny mice's new collagen scaffolding was similar to that in healthy skin. By day 21, the spiny mice were growing brand new hairs to replace the ones they had lost.
[caption id="attachment_379" align="alignright" width="270" caption="Unwounded spiny mice (top row); with large open wounds (middle); and after 30 days of healing. (Credit: Ashley Seifert et al, Nature)"][/caption]
Even more impressive was the mice's ability to heal 4 millimeter holes in their ears: they quickly closed the holes with new skin, regenerating hairs, fat cells and cartilage—but not muscle—without any scar tissue. In contrast, typical mice that Seifert tested failed to seal the wounds in their ears, forming scars instead. The results were published in Nature (Scientific American is a part of Nature Publishing Group).
When salamanders and newts regenerate an entire limb—a process known as epimorphic regeneration—one of the first steps is the formation of a blastema, a mass of cells that revert to an immature, undifferentiated state so that they are versatile enough to become the many different kinds of tissues in the new limb. Seifert observed clumps of unspecialized cells surrounding the spiny mice's ear wounds that looked very much like genuine blastemas: "Having done plenty of work on salamanders and such, what I saw in the mice looked almost identical. My colleagues and I were saying, 'This looks like a mammalian blastema!' You could see a conveyor belt of new hair follicles growing in the ear and undifferentiated cells—all the hallmarks of regeneration seemed to be there." In future work, Seiffert wants to examine these cells in more detail to confirm their true identity.
In past studies, scientists discovered that part of the reason Murphy Roths Large mice can regenerate ear tissue is not that they have a mutant gene or an additional gene, but rather that they do not express a particular gene known as p21. In related research, scientists reverted mouse muscles cells to a blastema-like state of immaturity by temporarily knocking out two tumor-suppressing genes. Extending the logic of these findings, p21 and other genes may suppress latent regenerative abilities in typical mice and indeed in most mammals. Learning to precisely control these genes at will opens the prospect of healing injuries in people by restoring our lost power of tissue regeneration. African spiny mice now offer scientists new opportunities to investigate such possibilities.