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Regenerating Rodent

An African mouse can regenerate wounded skin without scarring, providing insight into how tissue regeneration can occur in mammals.

By | September 26, 2012

image: Regenerating Rodent African spiny mice. Wikimedia Commons, Ltshears

Certain species of amphibians and reptiles easily regrow limbs after losing them in times of danger, but tissue regeneration is much more limited in mammals. Now, researchers describe a species of African mouse that can slough off and regrow skin tissue—including hair follicles—as good as new, possibly helping the animal evade predators. Published today (September 26) in Nature, the research offers scientists a new model for studying mammalian tissue regeneration.

The results are “interesting and amazing,” showing that the African spiny mouse “has the capacity to heal very large wounds,” said molecular biologist Ken Muneoka, who studies mammalian tissue regeneration at Tulane University but was not involved in the study.

The ability to lose and regenerate tissue, known as autotomy, is a well-studied phenomenon. Certain species of amphibians easily regenerate full limbs after amputation. Some lizards use autotomy as a survival tactic, having evolved tails that break off easily but continue wriggling to distract the predator. This allows the lizards to escape, and the animals simply regenerate their tails later.

But animals that branched later on the tree of life—like birds and mammals—have little, if any, ability to regenerative, explained Tara Maginnis, who studies the evolution of autotomy at the University of Portland but did not participate in the research. No adult mammals can regrow limbs, though a few rudimentary examples of regeneration do exist. Some species of mice, for instance, can shed the outer layer of skin from their tails to escape predation, and deer antlers are lost and re-grow on a yearly basis. A few species of mice can also regrow digit tips as well.

The current study was motivated by anecdotes from ecologists working in Kenya, who reported that African spiny mice (so-called because of large, spiny guard hairs on their backs) are difficult to handle, said first author Ashley Seifert of the University of Florida, who had investigated autotomy in amphibians. “They told me that their skin would tear easily. Huge portions of their skin detached, and the animals would take off running,” he explained. Intrigued, Seifert traveled to Kenya to investigate.

Working with colleagues at the University of Nairobi and the University of Wyoming, Seifert examined how African spiny mouse skin is constructed to allow it to pull away so easily. Lizards lose their tails at “fracture planes”—structural weak spots that break when the reptiles squeeze their muscles, encouraging the tail to fall away at a specific point. But African spiny mouse skin has no fracture planes, and unlike other species that lose the outer layer of skin from their tails, spiny mice lose large patches of skin, often exposing the muscle below.

Seifert and his colleagues found that compared to Mus musculus, the common laboratory mouse model, spiny mice skin is less elastic, probably because of the large hair follicles that take up about 12.5 percent more space than M. musculus hair follicles. Such large follicles reduce the space available for elastic connective tissue, making spiny mouse skin easier to tear.

When Seifert compared the regrowth of tissue in spiny mice to the lab specimens, he found that not only did epithelial cells migrate to the wound faster in spiny mice, but they did not scar. In M. musculus, collagen fibers arranged into dense, organized bundles that give rise to healed, but scarred, wounds. In contrast, the regenerating wounds of the spiny mouse had a looser collagen organization characteristic of undamaged tissue. Spiny mice also regrew their hairs, seemingly as a result of the same signals used in developing hair follicles;  M. musculus mice do not regrow hair.

“This provides conclusive evidence that these [spiny mice] can fully regenerate, and not just heal, complex cell and tissue types,” said Maginnis. Furthermore, modifying the hair follicle to elastic tissue ratio is “an entirely novel way of losing a chunk of tissue—not seen in other animals,” she noted, pointing out that for mice, which are nabbed by predators grasping their necks, losing tissue in this way may provide similar survival benefit as a lizard losing its tail.

As it happens, this isn’t the spiny mouse’s only regenerative trick. Another well-studied regeneration model is rabbits’ ability regenerate ear punches. It turns out that spiny mice can do the same. Seifert and his colleagues found that the mice can regenerate all tissue except muscle, an ability that appears to stem from a specialized conglomerate of de-differentiated cells, called the blastema, that initiates limb regeneration in other species.

In the future, Seifert plans to explore how the pathways regulating regeneration in the spiny mouse are modulated to produce tissue regrowth instead of scarring. It may be possible, he said, to modulate the immune response, in conjunction with other strategies, to push healing away from scar production towards a regenerative pathway.

Meanwhile, the findings should prompt other regeneration scientists to look more closely at their own regeneration models, said Stephen Badylak, deputy director of the McGowan Institute for Regenerative Medicine at the University of Pittsburgh, who did not participate in the research. “Some of the findings made me think we should reexamine our own results [in mice] and see if we had similar events going on,” said Badylak. “We’ve observed similar epithelial changes without really knowing why, and now they’re helping us understand what it means.”

A. W. Seifert et al., “Skin shedding and tissue regeneration in African spiny mice (Acomys),” Nature, 489:561-566, 2012.

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Comments

September 27, 2012

Gee, I learned long ago (college biology, back in the mid-'60's) about the ability of rodents to regenerate tissues. Go learn about rodents' teeth, for example.

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