17 March 2010

Organ regeneration: disable the p21 gene

Researchers from Wistar University in Philadelphia have found that turning off a single gene allows mammals to restore lost body parts, as happens, for example, in some amphibians.

The amazing properties of Murphy Roths Large (MRL) mice were discovered by chance in 1996, when the head of the current study, Ellen Heber-Katz, studied the features of the development of autoimmune diseases. To mark the animals, holes were made in the ear, which, as a rule, remain for life. To the surprise of scientists, the holes in MRL mice have grown without a trace in a few weeks.

(In the pictures found on the website toptenz.net , in the left column – holes in the ear of an ordinary mouse taken at regular intervals, in the right – in the mouse of the MRL line).

When studying the ability of MRL mice to regenerate, it turned out that they are not able to grow a limb entirely, but their damaged fingers are restored, and wounds heal much faster than in ordinary mice. It remained to understand why this was happening and whether it was possible to count on reproducing this effect.

The researchers started working in two directions at once. With the participation of colleagues from other research institutions in the USA, they began mapping the genome of the MRL line to determine the genes most likely responsible for tissue repair. Secondly, the scientists drew attention to the fact that the cells involved in regeneration are similar in their characteristics to embryonic stem cells, and began to study the effect of changes in DNA on the cell division cycle. It turned out that the p21 gene involved in the regulation of the cell division cycle is inactive in MRL mice. Normally, this gene inhibits cell division when their DNA is damaged in order to prevent malignant degeneration.

According to Professor Heber-Katz, mice with inactive p21 have a combination of rapid cell division, which restores tissues, and their equally rapid apoptosis (programmed death). This combination is observed in all animal species capable of regenerating lost body parts.

To test their hypothesis about the role of p21 in the process of tissue regeneration, biologists used another line of mice, also with the p21 gene turned off, but whose ability to accelerate wound healing was not noticed by anyone. The result confirmed the hypothesis of scientists.

Unfortunately, it is not yet necessary to talk about clinical studies of drugs that can accelerate the regeneration processes by suppressing the expression of the p21 gene: accelerated cell division can cause their malignancy. It is encouraging that in both lines of animals deprived of the p21 gene, the incidence of cancer was not higher than average. But in order to learn how to selectively accelerate the recovery of healthy cells without stimulating malignant ones, scientists will need time to conduct additional experiments.

Article by Khamilia Bedelbaeva et al. Lack of p21 expression links cell cycle control and appendage regeneration in mice is published in the journal PNAS.

Portal "Eternal youth" http://vechnayamolodost.ru based on PhysOrg materials: 1 gene lost = 1 limb regained?

17.03.2010

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