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This publication describes the application of the stable isotope labelling by amino acids in cell culture (SILAC) method to the whole mouse organism. Mice were fed with a special diet, in which the common 12C6-lysine, referred to as “light”, was replaced by “heavy” lysine labelled with 13C6 carbon. We were able to breed mice that were fully labelled with the heavy amino acid. This approach allows a quantitative analysis of whole proteomes by mass spectrometry. By applying this method to different genetically modified mice, it is possible to investigate the consequences of mutant genes on the proteome of distinct cell types within the whole mouse organism. By this method cell types can be analysed, which cannot be labelled in culture.

First we show that wild-type and β1 integrin deficient platelets have comparable proteomes with the exception that the integrin β1 and its dimerizing α subunits α2 and α6 are absent. Studies of hearts lacking β-parvin expression elucidate that upregulation of α-parvin expression compensates for the loss of β-parvin. Furthermore, analyses of kindlin-3 deficient erythrocytes reveal severe structural membrane defects. The mutant erythrocytes have an altered composition of membrane and cytoskeletal proteins and we found an almost complete absence of the proteins ankyrin-1, band 4.1, adducin-2, and dematin in membrane fractions of erythrocytes.