Mice deficient in desmin, the muscle-specific member of the intermediate 
filament gene family, display defects in all muscle types and particularly in 
the myocardium. Desmin null hearts develop cardiomyocyte hypertrophy and dilated 
cardiomyopathy (DCM) characterized by extensive myocyte cell death, calcific 
fibrosis and multiple ultrastructural defects. Several lines of evidence suggest 
impaired vascular function in desmin null animals. To determine whether altered 
capillary function or an intrinsic cardiomyocyte defect is responsible for 
desmin null DCM, transgenic mice were generated to rescue desmin expression 
specifically to cardiomyocytes. Desmin rescue mice display a wild-type cardiac 
phenotype with no fibrosis or calcification in the myocardium and normalization 
of coronary flow. Cardiomyocyte ultrastructure is also restored to normal. 
Markers of hypertrophy upregulated in desmin null hearts return to wild-type 
levels in desmin rescue mice. Working hearts were perfused to assess coronary 
flow and cardiac power. Restoration of a wild-type cardiac phenotype in a desmin 
null background by expression of desmin specifically within cardiomyocyte 
indicates that defects in the desmin null heart are due to an intrinsic 
cardiomyocytes defect rather than compromised coronary circulation.