Institut for Biomedicin

Lars Bolund

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

Publikation: Bidrag til tidsskrift/Konferencebidrag i tidsskrift /Bidrag til avisTidsskriftartikelForskningpeer review

DOI

  • Nicklas Heine Staunstrup
  • Karin Stenderup
  • Sidsel Mortensen, Department of Skin Inflammation Pharmacology, LEO Pharma, 2750 Ballerup, Denmark.
  • ,
  • Maria Nascimento Primo
  • ,
  • Cecilia Rosada
  • ,
  • Torben Steiniche
  • Ying Liu
  • ,
  • Rong Li
  • ,
  • Mette Schmidt, Department of Veterinary Reproduction and Obstetrics, Faculty of Life Sciences, University of Copenhagen, 1870 Frederiksberg C, Denmark., Danmark
  • Stig Purup
  • Frederik Dagnæs-Hansen
  • ,
  • Lisbeth Dahl Schrøder
  • ,
  • Lars Svensson, Department of NME Ideation, LEO Pharma, 2750 Ballerup, Denmark.
  • ,
  • Thomas Kongstad Petersen, Department of Skin Inflammation Pharmacology, LEO Pharma, 2750 Ballerup, Denmark.
  • ,
  • Henrik Callesen
  • Lars Bolund
  • Jacob Giehm Mikkelsen

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.

OriginalsprogEngelsk
TidsskriftDisease Models & Mechanisms
Vol/bind10
Sider (fra-til)869-880
Antal sider12
ISSN1754-8403
DOI
StatusUdgivet - 1 jul. 2017

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