Suprabasal integrin expression in the epidermis of transgenic mice results in developmental defects and a phenotype resembling psoriasis.
Integrin expression is normally confined to the basal layer of the epidermis, but when epidermal homeostasis is perturbed, the receptors are also expressed by suprabasal, differentiating keratinocytes. We have used the involucrin promoter to express functional human integrin subunits alpha 2, alpha 5, and beta 1 in the suprabasal epidermal layers of transgenic mice. In mice expressing alpha 5 or beta 1 alone or alpha 2 beta 1 or alpha 5 beta 1 heterodimers, there were hair and whisker abnormalities and a failure of eyelid fusion. In addition, mice expressing beta 1 alone or in combination with alpha 2 or alpha 5 exhibited epidermal hyper-proliferation, perturbed keratinocyte differentiation, and skin inflammation, all of which are features of a common human skin disease, psoriasis.
Carroll
J M
JM
Keratinocyte Laboratory, Imperial Cancer Research Fund, London, England.
Romero
M R
MR
Watt
F M
FM
D000818:Animals; D002448:Cell Adhesion; D002454:Cell Differentiation; D002455:Cell Division; D003433:Crosses, Genetic; D005314:Embryonic and Fetal Development; D004817:Epidermis / Q000254:growth & development / Q000378:metabolism* / Q000473:pathology; D005143:Eyelids / Q000002:abnormalities; D006197:Hair / Q000002:abnormalities; D006706:Homeostasis; D006801:Humans; D016023:Integrins / Q000096:biosynthesis* / Q000235:genetics; D015603:Keratinocytes / Q000166:cytology / Q000378:metabolism*; D051379:Mice; D008822:Mice, Transgenic; D011401:Promoter Regions, Genetic / Q000235:genetics; D011498:Protein Precursors / Q000096:biosynthesis / Q000235:genetics; D011565:Psoriasis / Q000209:etiology* / Q000473:pathology; D012867:Skin / Q000473:pathology; D012868:Skin Abnormalities; D014738:Vibrissae / Q000002:abnormalities
D016023:Integrins; D011498:Protein Precursors; C032253:involucrin