One Gene Lost = One Limb Regained? Scientists Demonstrate Mammalian Regeneration Through a Single Gene Deletion

Once again it seems that science will be furthered by scientist stumbling on a pebble which would send them down a path not yet plotted. While conducting an autoimmunity experiment in 1996 using MRL (Murphy Roth Large) mice, Dr. Haber-Katz ran into a snag. A few weeks into the experiment, the holes pierced through the ears of the mice which were used for long term identification, were healed without a trace. This discovery sent the scientist of the lab into a scramble to determine what made these mice heal with no scars. The lab went in two different directions: one focused on the mapping of the critical genes that accomplished this feat, while the second concentrated of the behavior of the cells. Almost immediately, the scientist noticed the cells of the MRL mice were atypical, demonstrating differences in cell cycle properties as well as DNA damage. It was soon found that p21, a cell cycle regulator, was inactive in the cells of the ear of the mice. In normal cells, p21 blocks the cell cycle in the event of DNA damage. This blocking prevents these damaged cells from dividing and potentially becoming cancerous. It was for this reason that the scientists worried that by removing the p21 gene they would see a rise in cancer. While there was an increase in damaged cells there was no increase in cancer cells. This was attributed to an increase in apoptosis in the cells with the p21 gene removed. The increase of the regenerative cells and the increase in apoptosis allowing rapid division of cells without the loss of control"… is similar to what is seen in mammalian embryos, where p21 also happens to be inactive after DNA damage. Unlike most mammals, which heal by scarring, these mice heal by “…forming a blastema, a structure associated with rapid cell growth and de-differentiation as seen in amphibians.” "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," said the project's lead scientist Ellen Heber-Katz, Ph.D., a professor in Wistar's Molecular and Cellular Oncogenesis program.

The Wistar Institute. "One Gene Lost = One Limb Regained? Scientists Demonstrate Mammalian Regeneration Through a Single Gene Deletion." ScienceDaily 16 March 2010. 24 March 2010 .