Fig. 9. Immunohistology revealed distinct changes in the expression of keratins and CE proteins in CTSD-deficient mice. Keratin K1 staining in healthy skin is only found in suprabasal layers of the epidermis, whereas keratin K5 is only expressed in epidermal basal cells. In CTSD^(–/–) mice there is a focal extension of K1 staining to the basal layer and a focal extension of K5 to the upper epidermal layers. Keratin K6 was faintly stained in normal mouse skin, but not in CTSD^(+/–) or CTSD^(–/–) mouse skin. Involucrin and filaggrin antibodies showed strong staining of the upper stratum spinosum and the stratum granulosum, whereas the loricrin antibody showed staining of the stratum granulosum solely in wild-type mouse skin. For all three antibodies staining intensity was reduced in CTSD^(+/–) mice and even more reduced in CTSD^(–/–) mice.