KCNN4 and Hyperkeratosis: To test the hypothesis, we generated conditional KCa3.1-overexpressor mice (KCa3.1+) that harbor a murine Kcnn4-transgene under the control of a tetracycline response element (TRE) together with a rtTA-transgene [40] for DOX-inducible Kcnn4-transgene expression specifically in epithelia including the epidermis (Fig 1A) and found that KCa3.1-induction causes eczematous dermatitis characterized by intra-epidermal edema (spongiosis), epidermal hyperplasia and hyperkeratosis, severe itch, and ulcers.