Proteomic analysis of Rac1 transgenic mice displaying dilated cardiomyopathy reveals an increase in creatine kinase M-chain protein abundance

Mol Cell Biochem. 2003 Sep;251(1-2):145-51.


Here, we demonstrate the application of the proteomic approach to the study of a transgenic mouse model of heart failure and provide an example of a disease-associated protein alteration that can be observed using this approach. Specifically, we applied the proteomic approach to the analysis of a mouse model of dilated cardiomyopathy in which the small GTPase, Rac1, was constitutively expressed specifically in the myocardium. We utilized the methods of two-dimensional gel electrophoresis (2-DE) for protein separation, silver-staining for protein visualization and mass spectrometry (MALDI-TOF and MS/MS) for protein spot identification. Computer-generated composite images were created which represent a normalized average of four 2-DE gel images derived from analysis of either Rac1 transgenic (n = 4) or non-transgenic (n = 4) mice. Analysis of composite images derived from NTG and Rac1 experimental groups revealed numerous statistically significant differences in mean protein spot intensities. Here, we report a statistically significant increase, of approximately 1.6-fold, in the mean protein spot intensity for creatine kinase M-chain in the composite image of Rac1 transgenic mice compared to control. This protein alteration may be consistent with an end-stage heart failure phenotype in which maximal myocardial reserve is employed to sustain survival.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cardiomyopathy, Dilated / enzymology*
  • Cardiomyopathy, Dilated / metabolism
  • Creatine Kinase / analysis*
  • Creatine Kinase / metabolism
  • Electrophoresis, Gel, Two-Dimensional
  • Gene Expression
  • Heart Failure / metabolism
  • Image Processing, Computer-Assisted
  • Mass Spectrometry
  • Mice
  • Mice, Transgenic*
  • Myocardium / enzymology
  • Myocardium / metabolism
  • Myosin Light Chains / analysis*
  • Myosin Light Chains / metabolism
  • Proteomics*
  • Silver Staining
  • Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
  • rac1 GTP-Binding Protein / analysis*
  • rac1 GTP-Binding Protein / metabolism


  • Myosin Light Chains
  • Creatine Kinase
  • rac1 GTP-Binding Protein