Tazarotene induces epidermal cell differentiation in the mouse tail test used as an animal model for psoriasis

Disturbed epidermal proliferation and keratinization are major features of psoriatic skin lesions. The so-called mouse tail test is known as an animal model to evaluate the antipsoriatic efficacy of topical drugs with regard to the induction of orthokeratosis. The purpose of the present study was to investigate the effect of tazarotene, a novel, receptor-specific retinoid, by the mouse tail test in a direct comparison to dithranol representing a classical topical antipsoriatic compound. The tails of CFLP mice were treated with tazarotene gel (0.1%, 0.05%), dithranol ointment (1.0%), tretinoin cream (0.05%) and methylcellulose (5%) hydrogel (vehicle control) for 2 weeks. Longitudinal histological sections were prepared from the tail skin, and the degree of orthokeratosis was determined by measuring the horizontal length of the fully developed granular layer within an individual scale in relation to its total length according to a method originally described by Bosman and co-authors. The degree of orthokeratosis was significantly (p < or = 0.05) increased by 0.1% tazarotene (87+/-20%), 1.0% dithranol (75+/-26%), 0.05% tazarotene (59+/-27%), and 0.05% tretinoin (23+/-13%) as compared to untreated (11+/-6%) and methylcellulose hydrogel-treated (13+/-6%) controls. Under the conditions of the mouse tail test, tazarotene showed a strong potency to induce orthokeratosis. With regard to clinically relevant concentrations this effect was even more pronounced than that observed for dithranol.