An animal model for keratosis

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Ichtyosis and psoriasis are the most common skin diseases with charactaristic clinical features of hyperkeratosis or keratosis. There is no define animal models for these diseases. Retinoic acid or its derivative, retinoids, are commonly used as a therapeutic drug, whereas there is no drug estimation model in animals in the meanings of animal model of the diseases. Our aid is a construction of transgenic mice with tissue specific expression of a point mutated retinoic acid receptor which has dominant-negative effect to the endogenous retinoic acid receptors. We constructed the plasmid vector with K14 promoter ligated to point mutated retinoic acid receptor cDNA.The resultant transgenic mice showed a epidermal specific expression of a point mutated retinoic acid receptor. Differentiation markers, such as keratins, are examined by purifying keratins from the transgenic mice and control mice. SDS-PAGE revealed that the wild type epidermis conatins K1, K5, K10 and K14, whereas transgenic mice skin showed K1, K5, K10, K14, K6 and K16. These abnormal expression of keratins mimics psoriasis skin. Expression pattern of keratins were examined by immunofluorescent study by using mono-specific anti-keratin antibody. In normal mice, K5/K14 are expressed only in basal cell layrs and reciprocally, K1/K10 are expessed above the basal cell layr. In the transgenic mice skin, K5/K14 are expressed on basal cell layr and one layr above the basal cell layr. K5/K14 are expressed from two layrs above the basal cell layr. These expression pattern of keratins are same to those observed in psoriasis. In the microscopic examination, the skin revealed the thinning of malpigi layr and the loose of rete ridge formation at the basement mombrane zone. These microscopic phenotype are different from those known human skin diseases.