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

Autor: Staunstrup, Nicklas Heine, Stenderup, Karin, Mortensen, Sidsel, Primo, Maria Nascimento, Rosada, Cecilia, Steiniche, Torben, Liu, Ying, Li, Rong, Schmidt, Mette, Purup, Stig, Dagnæs-Hansen, Frederik, Schrøder, Lisbeth Dahl, Svensson, Lars, Petersen, Thomas Kongstad, Callesen, Henrik, Bolund, Lars, Mikkelsen, Jacob Giehm
Zdroj: Disease Models and Mechanisms; July 2017, Vol. 10 Issue: 7 p869-880, 12p
Abstrakt: 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.
Databáze: Supplemental Index