The top two photos show the healing of ear holes in mice that have the p21 gene, after five days and 35 days. The bottom two pictures show the healing in mice that lack the p21 gene. (PNAS)Geneticists have found that the removal of a single gene allows mice to regenerate damaged body parts, as some salamanders do, a discovery that could one day lead to faster healing in humans.
The U.S. researchers found that the absence of one gene, called p21, allowed the mice to heal wounds without forming a scar, a method of healing usually seen only in animals like flatworms, sponges and newts.
"Much like a newt that has lost a limb, these mice will replace missing or damaged tissue with healthy tissue that lacks any sign of scarring," study leader Ellen Heber-Katz, a professor at Philadelphia's Wister Institute, said in a prepared statement.
Instead of a scar, the damaged tissue in these mice forms a blastema, a structure containing rapidly growing cells that behave more like embryonic stem cells than adult cells.
"While we are just beginning to understand the repercussions of these findings, perhaps, one day we'll be able to accelerate healing in humans by temporarily inactivating the p21 gene," said Heber-Katz.
Heber-Katz's lab first found in 1996 that a certain strain of mice, called Murphy Roths Large (MRL) mice, had remarkable healing abilities. When the researchers cut holes in the mice's ears, a common practice to identify specimens in experiments, they found that the holes soon closed without a trace of scarring.
The MRL mice also showed some partial regeneration of amputated digits and the articular cartilage that covers bones.
Genes mapped
The Wister researchers, in collaboration with geneticists at Drexel University and Washington University, began mapping which genes were involved in the mice's healing ability.
Two researchers at Wister, Khamilia Bedebaeva and Andrew Snyder, investigated the unusual cell cycles of the MRL mice and found that the gene p21 was inactive in the damaged mouse ear cells.
The p21 gene is a cell cycle regulator, and the researchers found that mice lacking this gene had the same regenerative qualities as the MRL mice.
"In normal cells, p21 acts like a brake to block cell cycle progression in the event of DNA damage, preventing the cells from dividing and potentially becoming cancerous," Heber-Katz said.
"In these mice without p21, we do see the expected increase in DNA damage, but surprisingly no increase in cancer has been reported," she said.
The findings were reported this week in Proceedings of the National Academy of Sciences.
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