Losing Your Skin to Gain Your Life


Regenerative medicine can find tips in the oddest corners of biology, and today’s tip is no different. African spiny mice (Acomys) are very unusual critters among mammals. Apparently some people like to keep them as pets, but other types of mammals find the mice rather tasty. If a predator gets its teeth into the mouse, pieces of the spiny mouse’s hide rip off in the mouth of the attacker, and the rodent runs free to live another day. Disgusting? The mouse gets the best end of the deal because its skin grows back almost as good as new. This discovery provides a viable model for the study of regeneration in a mammal, and since humans are mammals, such studies can apply to human regeneration.

Some lizards, salamanders, sea cucumbers, crustaceans, and other types of arthropods (insects, crabs, lobsters, and so on) have the ability to lose a body part to avoid capture and then replace it. Unfortunately, until now, this ability was completely unknown in mammals.

Developmental biologist Ashley Seifert of the University of Florida in Gainesville and his colleagues had their interest piqued when they heard rumors about an African mouse that could grow back its skin. The African spiny mouse is a rodent with stiff hairs on its back that resemble the spines of a hedgehog. Since the animal is kept as a pet by some people, owners have noticed that the animal has a tendency to lose patches of skin when handled.

Seifert and his colleagues were able to find the spiny mouse in the wild in parts of Kenya. When they took the animals into the laboratory, they discovered that spiny mice have skin that is 20 times weaker than the skin of standard laboratory mice. The weakness of the spiny mouse’s skin might result from the very large hair follicles. Further work with the spiny mouse showed that the animal’s wounds heal faster than those of standard laboratory mice. In addition to increase speed of healing, the skin heals without forming scar tissue, and even replaces the hair follicles after an injury.

The photograph comes from Ashley W. Seifert, Stephen G. Kiama, Megan G. Seifert, Jacob R. Goheen, Todd M. Palmer & Malcolm Maden, (2012) Skin shedding and tissue regeneration in African spiny mice (Acomys) Nature 489: 561–565.

How much skin can this animal replace at a time? Seifert’s team showed that African spiny mice can survive the loss of 60% of the skin off their backs and still regenerate it and bounce back. Elly Tanaka, who works as a developmental biologist at the Technical University of Dresden in Germany, but was not involved with the work, said: “It seems remarkable that an animal can lose so much skin and heal the skin so well that it looks normal,” Tanaka has a point. There are a few species of lizard that can shed their skin in a hurry as an escape response. For example, Anguis fragilis, a legless lizard can shed patches of its skin to escape a predator. In this case, however, only the top layer of skin falls off and the lower layers of skin regrow the upper layers. In the case of the African spiny mouse, however, the animals lose their entire skin with all its layers. Nothing remains but bare muscles, which makes the replacement of the skin a much more daunting process. “It’s a nice example that shows the maximum capacity of what the mammalian skin can do in terms of healing,” Tanaka says.

Seifert and his team investigated the mechanism of regeneration in spiny mice by punching holes in their ears. They discovered that regeneration in the ears mimicked limb regeneration in newts. Upon injury, the mouse’s body generates a population of embryonic-like cells that aggregate underneath the layer of cells that first cover the wound. These embryonic-like cells divide and differentiate into the different cell types that will re-form the ear tissue.

“It is truly exciting to discover that these mammals are capable of losing and regrowing complex tissue in such an efficient manner,” says Tara Maginnis, an evolutionary biologist at the University of Portland in Oregon who was not involved with the work. “It’s another ‘gripping’ example of how organisms can evolve alternative, adaptive traits not by inventing new structures or pathways but by modifying existing structures” such as the skin, she says.

Regeneration is not unheard of mammals, since rabbits also have the ability to replace bit of their ears is they go missing, and deer can regrow their antlers. However the ability to regrow large swaths of e lost skin is unique among mammals. In the words of University of Utah molecular biologist Shannon Odelberg, this constitutes a “surprising example of mammalian regeneration.” Odelberg continued: “This discovery puts scientists one step closer to being able to unravel the molecular bases of regeneration in vertebrates and possibly translating these discoveries into therapies.”

Let’s think about this for a while. These mice almost certainly have a genome that is not all that different from that of other mice. The differences are due to the way those genes are regulated. If we could truly understand how these mice get their cells to revert to an embryonic-like state and spread out to heal wounds, we could offer therapies to burn patients that could repair over 60% of their skin. Think of it. This would be nothing short of biblical.

This nicely illustrated why basic scientific research is so important, and why is must continue to occur. Model systems matter.

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mburatov

Professor of Biochemistry at Spring Arbor University (SAU) in Spring Arbor, MI. Have been at SAU since 1999. Author of The Stem Cell Epistles. Before that I was a postdoctoral research fellow at the University of Pennsylvania in Philadelphia, PA (1997-1999), and Sussex University, Falmer, UK (1994-1997). I studied Cell and Developmental Biology at UC Irvine (PhD 1994), and Microbiology at UC Davis (MA 1986, BS 1984).