Scientists discovered how to express utrophin, which could replace defective dystrophin in diseased patients.
Researchers at the University of Pennsylvania School of Medicine report how the gene for utrophin, which codes for a protein very similar to dystrophin, the defective protein in Duchenne muscular dystrophy (DMD), puts the brakes on its own expression in muscle cells.
The production of utrophin slows in fetal muscles soon after birth, after which dystrophin takes over as the primary muscle-associated protein. If this process could be prevented, then increased utrophin could substitute for dystrophin as a possible therapy for DMD. Utrophin is over 80% identical to dystrophin.
In the present study, the scientists discovered that silencing is applied by a protein called Ets-2 repressor factor (ERF) situated on a small piece of the utrophin gene called the N-box. When the N-box was deleted from the utrophin gene, ERF had no effect on silencing the utrophin gene, as measured by an increase in utrophin gene-promoter activity. In another experiment in which ERF was repressed, the researchers found utrophin mRNA production increased.
The findings were published online in Molecular Biology Cell in advance of print publication.