الفهرس 
IntroductionOnly 14 pages are availabe for public view
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Abstract
FSHD is a muscle dystrophy disease that affects certain muscle groups in the body. As the disease progresses, 20% of the patients become wheelchaired. It has been agreed that the disease is caused by an abnormal expression of a protein called DUX4. This protein causes cell death and inhibit muscle differentiation.
This study represents a screen of 1972 miRNA-inhibitors for their effect on the cell death induced by doxycycline inducible DUX4 gene in a transgenic cell line. The cells used for the screen were human myoblast LHCN-M2 cells. The study started by doing a transfection of the miRNA-inhibitors into human myoblast cells. This was followed by induction of DUX4 expression by the addition of doxycycline. The addition of doxycycline causes expression of DUX4 through a dox inducible system that has been previously generated in the cells. The expression of DUX4 causes cell death. Then a viability assay was done aiming for a protective effect of the previously transfected miRNA-inhibitors.
The study results showed a number of protective miRNA-inhibitors. Of these the most potent was miR-inh-3202. miR-inh-3202 was purchased and a number of assays was done as aimed in the study protocol. This included study of the protective effect of miR-inh-3202 against various forms of cytotoxicity that show a specifically protective effect against DUX4 pathology. A secondary screen was done on IPSCs derived human myoblasts generated from FSHD patients. The results of this final experiment showed that miRNA-3202 inhibition did not have any effect on the expression of DUX4 gene or the DUX4 target gene expression. This indicated that miRNA-3202 inhibition is working through a downstream mechanism. Further studies was done to detect the downstream mechanism through which miRNA-3202 inhibition produced its protection against DUX4 induced myoblast pathology