delanceyplace.com 3/19/10 - hope and the p21 gene

In today's excerpt - new hope for the regeneration of tissue in humans, based on
experiments with mice and similar in type to the regeneration of tissue and limbs
in creatures like newts, flatworms, and sponges:
"A quest that began over a decade ago with a chance observation has reached a milestone:
the identification of a gene that may regulate regeneration in mammals. The absence
of this single gene, called p21, confers a healing potential in mice long thought
to have been lost through evolution and reserved for creatures like flatworms, sponges,
and some species of salamander.
"In a report published in the Proceedings of the National Academy of Sciences, researchers
from The Wistar Institute demonstrate that mice that lack the p21 gene gain the
ability to regenerate lost or damaged tissue.
"Unlike typical mammals, which heal wounds by forming a scar, these mice begin by
forming a blastema, a structure associated with rapid cell growth and de-differentiation
as seen in amphibians. According to the Wistar researchers, the loss of p21 causes
the cells of these mice to behave more like embryonic stem cells than adult mammalian
cells, and their findings provide solid evidence to link tissue regeneration to
the control of cell division.
" '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. '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.'
"Heber-Katz and her colleagues used a p21 knockout mouse to help solve a mystery
first encountered in 1996 regarding another mouse strain in her laboratory. MRL
mice [a strain of mouse that exhibits remarkable regenerative abilities for a mammal]
which were being tested in an autoimmunity experiment, had holes pierced in their
ears to create a commonly used life-long identification marker. A few weeks later,
investigators discovered that the earholes had closed without a trace. While the
experiment was ruined, it left the researchers with a new question: Was the MRL
mouse a window into mammalian regeneration? ...
"[Researchers] found that p21, a cell cycle regulator, was consistently inactive
in cells from the MRL mouse ear. P21 expression is tightly controlled by the tumor
suppressor p53, another regulator of cell division and a known factor in many forms
of cancer. The ultimate experiment was to show that a mouse lacking p21 would demonstrate
a regenerative response similar to that seen in the MRL mouse. And this indeed was
the case. As it turned out, p21 knockout mice had already been created, were readily
available, and widely used in many studies. What had not been noted was that these
mice could heal their ears.
" '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.'
"
Science Daily , March 16, 2010, based on the article "Lack of p21 expression links
cell cycle control and appendage regeneration in mice," by Khamilia Bedelbaeva,
Andrew Snyder, Dmitri Gourevitch, Lise Clark, Xiang-Ming Zhang, John Leferovich,
James M. Cheverud, Paul Lieberman, and EllenHeber-Katz, from Proceedings of the
National Academy of Sciences of the United States of America, doi:10.1073/pnas.1000830107.