Psoriasiform skin disease in transgenic pigs with high-copy ectopic expression of human integrins α2 and β1
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Psoriasiform skin disease in transgenic pigs with high-copy ectopic expression of human integrins α2 and β1. / 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.
In: Disease Models & Mechanisms, Vol. 10, No. 7, 2017, p. 869-880.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - Psoriasiform skin disease in transgenic pigs with high-copy ectopic expression of human integrins α2 and β1
AU - Staunstrup, Nicklas Heine
AU - Stenderup, Karin
AU - Mortensen, Sidsel
AU - Primo, Maria Nascimento
AU - Rosada, Cecilia
AU - Steiniche, Torben
AU - Liu, Ying
AU - Li, Rong
AU - Schmidt, Mette
AU - Purup, Stig
AU - Dagnæs-Hansen, Frederik
AU - Schrøder, Lisbeth Dahl
AU - Svensson, Lars
AU - Petersen, Thomas Kongstad
AU - Callesen, Henrik
AU - Bolund, Lars
AU - Mikkelsen, Jacob Giehm
PY - 2017
Y1 - 2017
N2 - 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.
AB - 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.
KW - DNA transposition
KW - Integrin
KW - Pig cloning
KW - Psoriasis
KW - Skin inflammation
KW - Sleeping Beauty
U2 - 10.1242/dmm.028662
DO - 10.1242/dmm.028662
M3 - Journal article
C2 - 28679670
AN - SCOPUS:85027038285
VL - 10
SP - 869
EP - 880
JO - Disease Models & Mechanisms
JF - Disease Models & Mechanisms
SN - 1754-8403
IS - 7
ER -
ID: 184391478