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Dis Model Mech. 2017 Jul 1;10(7):869-880. doi: 10.1242/dmm.028662.

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

Author information

1
Department of Biomedicine, Aarhus University, 8000 Aarhus C, Denmark.
2
iPSYCH The Lundbeck Foundation Initiative For Integrative Psychiatric Research, Denmark.
3
iSEQ, Centre for integrative sequencing, Aarhus, Denmark.
4
Department of Dermatology, Aarhus University Hospital, 8000 Aarhus C, Denmark.
5
Department of Skin Inflammation Pharmacology, LEO Pharma, 2750 Ballerup, Denmark.
6
Department of Animal Science, Aarhus University, 8830 Tjele, Denmark.
7
Department of Veterinary Reproduction and Obstetrics, Faculty of Life Sciences, University of Copenhagen, 1870 Frederiksberg C, Denmark.
8
Department of NME Ideation, LEO Pharma, 2750 Ballerup, Denmark.
9
HuaDa JiYin (BGI), Shenzhen 518083, China.
10
Department of Biomedicine, Aarhus University, 8000 Aarhus C, Denmark giehm@biomed.au.dk.

Abstract

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.

KEYWORDS:

DNA transposition; Integrin; Pig cloning; Psoriasis; Skin inflammation; Sleeping Beauty

PMID:
28679670
PMCID:
PMC5536904
DOI:
10.1242/dmm.028662
[Indexed for MEDLINE]
Free PMC Article

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