Tuesday, 3 April 2012

Genetic Discovery & Human Regeneration

It is no secret that the ‘healing stage’ after any injury is a very slow and a painful process. Even after that, most of the times we are left with memorable scars to remind us of that eventful journey. So what if we are able to recover from an injury with the guarantee of no scars? Organisms such as newts and the axolotls are commonly known for having the ability to completely regenerate appendages without any visible scares but it was considered that this property was lost in mammals through evolution (2). However, recent studies lead scientists to believe that this ability may be reactivated in mammals, leading to ‘scar-free’ healing.
Description: mouseMammal’s usual method of wound healing is “the process of repair characterized by wound site contraction and closure with a scar” (1). However, a rare exception to this is the Murphy Roths Large Mouse, Commonly known as the MRL mouse. (Figure 1)
“The MRL mouse and its close relatives (“healer” strains) have unique healing and regenerative capabilities, including the complete closure and tissue regeneration of through-and-through ear hole puncture wounds with the formation of a circular blastema, the regrowth of articular cartilage, and the partial regeneration of amputated digits” (1).
Figure 1: MRL Mouse
Description: http://www.technovelgy.com/graphics/content05/mice-regrow.jpg
Figure 2: Differences of Ear hole healing in a normal and a MRL mouse
By examining many organisms with the ability to regenerate appendages, cell cycle variation was assumed as the possible cause of regenerative ability. Upon observations, distinct differences were found in regenerative and non-regenerative species in relation to the fraction of cells in the G2 and M phases of the cell cycle (2). In addition, DNA damage was observed in most of the cells of regenerative species. From these results, it was assumed that a possible G1 cell cycle checkpoint deficiency could be the defining factor of regeneration (2).
The kinase inhibitor protein is a key proteins that maintains a strong G1 Checkpoint (3). This inhibitor protein is dependent on two genes known as p53 and p21 (1, 3).  By further analyses, a lack of the p21 gene in healer cells were observed. To examine this, an experiment was carried out by engineering non healing mice to lack the p21 gene and creating holes in their ears, as explained in http://www.pnas.org.ezproxy.library.uq.edu.au/content/107/13/5845.full. These mice recovered with complete ear hole closure with no sign of scares (Figure 3). This confirmed that the p21 gene holds the key responsibly for regeneration (2). This lead them to believe that the regeneration process could be reactivated in mammals by temporarily switching off the p21 gene (1).
Figure 3: Ear closure of the p21 Deficient mouse

However, a few problems are bound to arise with forced genetic variations. In this case, the p21 acts as an anti-cancer mechanism and by switching it off, the DNA of mammals can be exposed to worsening damage. In addition, the p53 genes, a known regulator of cell division, are closely associated with the p21 gene in their functions. Hence, the p53 gene might be defected by switching off the p21 gene, exposing the mammals to many different types cancer (1). Even though there are a few down sides, these genetic discoveries may lead to further studies of the human regeneration process, leading to regeneration of appendages and ‘scar-free’ healing of injuries in the distant future. 
1.       Khamilia Bedelbaeva, Andrew Snyder, Dmitri Gourevitcha, Lise Clarka, Xiang-Ming Zhanga, John Leferovicha, James M. Cheverudb, Paul Liebermana, & Ellen Heber-Katza,3 Lack of p21 expression links cell cycle control and appendage regeneration in mice, Cell Biology, volume 107, viewed 6th September 2011, http://www.pnas.org.ezproxy.library.uq.edu.au/content/107/13/5845.full#ref-23
2.       Caroline Davies, ‘Genetic Discovery Promises Healing without no scares’, The Guardian, viewed 6th September 2011, http://www.guardian.co.uk/science/2010/mar/15/mice-genetics-p21-heal-no-scar
3.       Campbell NA, Reece JB, Meyers N, Urry LA, Cain ML, Wasserman SA, Minorsky PV and Jackson, RB (2009). Biology 8th Edition, Australian Version. Persons Education, Sydney.

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