Abstract

The MRL mouse is an inbred laboratory strain, which was developed in the 60’s of the 20th century and has been extensively used as a model of lupus erythematosus. The regenerative abilities of the strain were discovered in the 90' when the MRL mouse was shown to close 2 mm hole punches made in the ear pinnae four weeks after injury without scarring. The phenomenon has not been observed in other mouse strains, where the holes remain for life. The process is accompanied by cartilage regrowth, normal vascularisation, the restoration of hair follicles and peripheral nerves. Enhanced regenerative response in the MRL mouse has been observed in heart after cryo-injury of the right ventricle, spinal cord following hemi-section, digits after amputation, and articular cartilage. A remarkable feature of the strain is that the MRL mice retain several foetal biochemical characteristics as adults, including increased expression of stem cell markers. The epigenetic regulation, though known to play a key role in the organ development, has not been examined with respect to regeneration. The idea of our project is to examine the epigenetic basis of regeneration by comparing genome-wide DNA methylation and expression profiles in two murine strains: the MRL mouse which displays enhanced regeneration abilities and the control C57BL/6J mouse. In our experiments we applied methylated DNA immunoprecipitation followed by the analysis using NimbleGen microarray platform (Roche) which covers all promoter regions in the murine genome. We examined the promoter methylation profiles in heart, liver and spleen samples. The preliminary results allowed us to extract a number of genes that show the most spectacular differences in the DNA methylation of promoter regions between the MRL and the control strain (i.e. 100% methylated and 100% unmethylated). Our particular interest is focused on these among the differentially methylated genes which display similar methylation pattern in the MRL mouse and murine embryonic stem cells. The microarray data are being verified by quantitative Real-Time PCR. We believe that the elucidation of the epigenetic basis of regeneration phenomenon in the MRL mouse will contribute to a better understanding of regeneration processes, as well as it may provide clues on how cross the limitations of regeneration in mammals.

Authors (5)