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

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 Dys^KI/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 Dys^KI mice to determine whether Dys^KI mice have less sarcolemmal membrane disruption and myocyte damage in CVB3 infection. Preliminary data showed no significant difference between Dys^KI 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 Dys^KI mice.