Within the framework of a pilot project on the analysis of the mouse proteome, we investigated C57BL/6 mice (Mus musculus), a standard inbred strain of the mouse, starting with the analysis of brain, liver and heart proteins. Tissue extraction and the separation of proteins were performed with techniques offering a maximum of resolution. Proteins separated were analyzed by mass spectrometry. Gene-protein identification was performed by genetic analyses using the European Collaborative Interspecific Backcross (EUCIB), established from the two mouse species Mus musculus and Mus spretus. On the basis of protein polymorphisms we mapped hundreds of genes on the mouse chromosomes, allowing us new insight into the relationship between genotype and phenotype of proteins. In particular, the results showed that protein modifications can be genetically determined, therefore representing their own class of protein phenotypes. In this context, results are discussed suggesting that phenotypes of single protein species may result from several genes. Accordingly, proteins are considered as polygenic traits. In contrast, one example demonstrates that proteins may also have pleiotropic effects: a single gene mutation (a single altered protein) may affect several other proteins. From these studies we conclude that gene-related functional proteomics will show in the future that genetic diseases, defined today by clinical symptoms and considered as etiological entireties, can be subdivided into different diseases according to different affected genes.