Dr. Byung Kwan Lim of the University of California in San Diego

Awarded grant in 2009

The Role of Dystrphin in Enterovirus Induced Viral Myocarditis

Dr. Byung Kwan Lim of the University of California in San Diego

Specific Aim1. Determine whether cardiac myocyte-specific, inducible expression of enterovirus protease 2A in the dystrophin knock-in adult mouse heart can prevent myocyte sarcolemmal membrane disruption and the subsequent development of cardiomyopathy.

Hypothesis: Dystrophin knock-in can prevent mycoyte sarcolemmal membrane disruption through inhibition of dystrophin cleavage by enterovirus protease 2A.

Expected Results: We will generate DysKI/2A/MCM triple transgenic mice to determine the effect of cleavage-resistant dystrophin in cardiac-specific inducible expression of enterovirus protease 2A.

Specific Aim2. Determine whether knock-in of dystrophin that prevent protease 2A cleavage of dystrophin can protect against CVB3 infection mediated cardiac myocyte damage and myocarditis. 

Hypothesis: Dystrophin knock-in reduces dystrophin cleavage and sarcolemmal membrane disruption after CVB3 infection.

Expected Results: We generated inbred Balb/C DysKI mice to determine whether DysKI mice have less sarcolemmal membrane disruption and myocyte damage in CVB3 infection. Preliminary data showed no significant difference between DysKI and littermate controls. There are similar virus titer and Evans blue dye uptake percent. However, Balb/C mice have high susceptibility to CVB3 and immune response. To prove a mechanical effect of virus infection we will generate less susceptible inbred C3H background DysKI mice.