Suprabasal integrin expression in the epidermis of transgenic mice results in developmental defects and a phenotype resembling psoriasis

Abstract

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.

Oligonucleotide cleavage and rejoining by topoisomerase III from the hyperthermophilic archaeon Sulfolobus solfataricus: temperature dependence and strand annealing‐promoted DNA religation

“…Of particular interest is the possibility that type IA topoisomerases play a role in resolving the intermediates of DNA replication and recombinational repair (e.g. Holliday or double Holliday junctions) through their association with RecQ-like DNA helicases, which have been found in bacteria (RecQ), yeast (Sgs1, Rqh1) and humans (BLM, WRN, RECQL, RECQ4 and RECQ5) (Irino et al, 1986;Gangloff et al, 1994;Puranam and Blackshear, 1994;Carroll et al, 1995;Ellis et al, 1995;Yu et al, 1996;Stewart et al, 1997;Cogoni and Macino, 1999;Kitao et al, 1999). Mutations in human RecQ homologues have been linked to diseases including Bloom, Werner and Rothmund-Thomson syndromes (Ellis et al, 1995;Yu et al, 1996;Kitao et al, 1999).…”

Regulation of Interleukin-1α Expression by Integrins and Epidermal Growth Factor Receptor in Keratinocytes from a Mouse Model of Inflammatory Skin Disease

“…To analyze the significance of suprabasal integrin expression, transgenic mice have been generated in which individual human integrin subunits are expressed under the control of the involucrin promoter (2,3). Mice expressing a ␤ 1 transgene (Inv␤ 1 mice) are crossed with mice expressing ␣ 2 , ␣ 3 , or ␣ 5 integrin transgenes (Inv␣ 2 , Inv␣ 3 , or Inv␣ 5 animals) to generate mice with the corresponding suprabasal integrin heterodimers: ␣ 2 ␤ 1 , ␣ 3 ␤ 1 , or ␣ 5 ␤ 1 .…”

Anti-CD11a Ameliorates Disease in the Human Psoriatic Skin–SCID Mouse Transplant Model: Comparison of Antibody to CD11a with Cyclosporin A and Clobetasol Propionate

“…No animal disease completely mimics psoriasis (Carroll et al, 1995;Sundberg et al, 1990). Keratinocytes and fibroblasts from psoriatic skin were isolated and studied in monolayer culture (Nickoloff et al 1989;Pellegrini et al, 1992;Priestley, 1987), and psoriatic lesional skin was studied in organ culture (Caron, 1968;Kondo, 1986;Kondo et al, 1992;Mils et al, 1994;Varani et al, 1998).…”