Proteomic Analysis of Loricrin Knockout Mouse Epidermis

The cross-linked envelope of the mammalian epidermal corneocyte is important as a scaffold for assembly of the lipid barrier of the epidermis. Illustrating its importance, deficient envelope cross-linking by keratinocyte transglutaminase (TGM1) is a major cause of the autosomal recessive congenital ichthyoses, characterized by barrier defects. Expectations that loss of some of the known envelope protein components would also confer an ichthyosis phenotype have been difficult to demonstrate. To help rationalize this observation with one major component, the protein profile of epidermis from loricrin knockout mice has been compared to that of the wild type. Despite the mild phenotype of the knockout, some 40 proteins have been seen to be incorporated into envelope material to significantly different extents. Nearly half of these proteins were also seen to be incorporated to similarly altered extents into the disulfide bonded keratin network of the corneocyte. The results suggest that loss of loricrin alters their incorporation into envelopes as a consequence of protein-protein interactions during cell maturation. Mass spectrometric protein profiling revealed that keratin 1, keratin 10 and loricrin are prominent envelope components and that dozens of other proteins are also components. This finding helps rationalize the potential formation of functional envelopes despite loss of a single component due to availability of many alternative transglutaminase substrates