Investigation of heart proteome of different consomic mouse strains. Testing the effect of polymorphisms on the proteome-wide trans-variation of proteins

•The proteomic network acts as a global disease modifier.•Protein–protein interaction must be well buffered to protect against a disease.•The genome is the database of the cell, the proteome the system of action.

We investigated to which extent polymorphisms of an individual affect the proteomic network. Consomic mouse strains (CS) were used to study the trans-effect of the cis-variant (polymorphic) proteins of the strain PWD/Ph on the proteins of the host strain C57BL/6J. The cardiac proteome of ten CSs was analyzed by 2-DE and MS. Cis-variant PWD proteins altered a high number of C57BL/6J proteins, but the number of trans-variant proteins differed considerably between different CSs. Cardiac hypertrophy was induced in CSs. We found that high variability of the proteome, as induced by polymorphisms in CS14, acts protective against the complex disease.

Graphical abstractThe influence on individual polymorphisms to the central (core) proteome which affect the disease phenotype. (A) Consomic mouse strains (B) to study the frequency of trans-variant proteins in the heart proteome and (C) their response to induced cardiac pressure overload. S. Forler, O. Klein, S. Köhler et al., EuPA Open Proteomics, 2015.Figure optionsDownload full-size imageDownload as PowerPoint slide