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
Department of Biomedicine, Aarhus University, 8000 Aarhus C, Denmark.
iPSYCH The Lundbeck Foundation Initiative For Integrative Psychiatric Research, Denmark.
Dis Model Mech. 2017 Jul 1;10(7):869-880. doi: 10.1242/dmm.028662.
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.
银屑病是一种复杂的人类特异性疾病，其特征为角质形成细胞增殖紊乱以及皮肤中存在促炎环境。猪的皮肤结构和免疫与人类非常相似，这使得猪成为研究银屑病生物学和治疗方法的合适动物模型。整合素的表达通常局限于表皮的基底层，但在银屑病皮肤的基底层上方角质形成细胞中持续存在，调节增殖、分化以及白细胞浸润。在此，我们培育了在表皮基底层上方共表达整合素α2和β1的小型猪。该项目中出生的整合素转基因小型猪表现出与插入转基因数量相关的皮肤表型。分子分析与银屑病特征的组织学观察结果高度一致，包括颗粒层减少和T淋巴细胞浸润。这些发现标志着首次创建了具有类似人类银屑病的银屑病样表型的小型猪，并证明整合素信号在银屑病病理过程中起关键作用。
