Bovine dilated cardiomyopathy: Proteomic analysis of an animal model of human dilated cardiomyopathy

Bovine hereditary dilated cardiomyopathy (bCMP) is endemic in Switzerland a nd hearts from diseased animals display important clinical and biochemical similarities to human DCM. Recent research has identified at least one prot ein (myoglobin) to be significantly reduced in bovine DCM. Using a proteomi c approach, we have separated over 1125 protein species from bovine ventric ular tissue. Gel analysis and protein characterisation have identified a nu mber of proteins whose abundance is significantly altered in bovine DCM. Tw enty-four proteins are of decreased abundance in diseased tissue, whilst 11 proteins are of increased abundance in the diseased state. A combination o f amino acid compositional analysis, peptide mass profiling, N-terminal mic rosequencing and Multildent (http://www.expasy.ch/sprot/multiident.html) ha s been employed in order to elucidate the identities of the differentially expressed proteins. Using these techniques we have currently determined the identity of 12 of the 35 altered proteins. We have also detected three pro teins that are differentially expressed in genotypically diseased but pheno typically normal animals, identifying a possible mechanism for the onset of the disease. The possibility that inappropriate ubiquination of proteins p lays an important role in the disease is discussed. A database of bovine pr oteins is currently being established. The identity of the proteins affecte d, together with a comparison of the human and bovine expression patterns, is displayed.