Psoriasiform skin disease in transgenic pigs with high-copy ectopic expression of human integrins α2 and β1

• Main Authors: Nicklas Heine Staunstrup, Karin Stenderup, Sidsel Mortensen, Maria Nascimento Primo, Cecilia Rosada, Torben Steiniche, Ying Liu, Rong Li, Mette Schmidt, Stig Purup, Frederik Dagnæs-Hansen, Lisbeth Dahl Schrøder, Lars Svensson, Thomas Kongstad Petersen, Henrik Callesen, Lars Bolund, Jacob Giehm Mikkelsen
• Format: Article
• Language: English
• Published: The Company of Biologists 2017-07-01
• Series: Disease Models & Mechanisms
• Subjects: DNA transposition; Integrin; Pig cloning; Psoriasis; Skin inflammation; Sleeping Beauty
• Online Access: http://dmm.biologists.org/content/10/7/869

Psoriasis is a complex human-specific disease characterized by perturbed keratinocyte proliferation and a pro-inflammatory environment in the skin. Porcine skin architecture and immunity are very similar to that in humans, rendering the pig a suitable animal model for studying the biology and treatment of psoriasis. Expression of integrins, which is normally confined to the basal layer of the epidermis, is maintained in suprabasal keratinocytes in psoriatic skin, modulating proliferation and differentiation as well as leukocyte infiltration. Here, we generated minipigs co-expressing integrins α2 and β1 in suprabasal epidermal layers. Integrin-transgenic minipigs born into the project displayed skin phenotypes that correlated with the number of inserted transgenes. Molecular analyses were in good concordance with histological observations of psoriatic hallmarks, including hypogranulosis and T-lymphocyte infiltration. These findings mark the first creation of minipigs with a psoriasiform phenotype resembling human psoriasis and demonstrate that integrin signaling plays a key role in psoriasis pathology.