Establishment of a Mouse Model of Atopic Dermatitis by Deleting Ikk2 in Dermal Fibroblasts

Abstract

Atopic dermatitis is a chronic inflammatory skin disease with persistent pruritus. To clarify its molecular mechanism, it is important to establish a mouse model similar to the phenotypes of atopic dermatitis patients, particularly in exhibiting scratching behavior. Ikk2, a component of the IκB kinase complex, exerts pro-inflammatory responses, whereas its deficiency in keratinocytes paradoxically causes skin inflammation. In this study, we sought to generate a mouse model exhibiting skin inflammation by which dermal fibroblasts lack Ikk2 expression and evaluate whether cutaneous inflammatory phenotypes are similar to those of atopic dermatitis patients. To generate Ikk2-deficient mice (Nestincre;Ikk2FL/FL) in which Ikk2 is deleted in dermal fibroblasts, we crossed female Ikk2FL/FL mice to male Nestincre;Ikk2FL/+mice. These mice spontaneously developed skin inflammation limited to the face, with the appearance of Ikk2-deficient fibroblasts in the facial skin. These mice showed phenotypes similar to those of atopic dermatitis patients, including scratching behaviors, which are resistant to immunosuppressive or molecularly targeted drugs. These findings suggest that the Nestincre;Ikk2FL/FL mouse is an atopic dermatitis model that will be useful in clarifying atopic dermatitis pathogenesis and in developing a novel therapeutic agent for atopic dermatitis symptoms.