The Jackson Laboratory, Bar Harbor, ME, United States of America.
Department of Comparative Pathobiology, College of Veterinary Medicine, Purdue University, West Lafayette, IN, United States of America.
PLoS One. 2020 Jul 20;15(7):e0235295. doi: 10.1371/journal.pone.0235295. eCollection 2020.
Spontaneous mutations in the SHANK-associated RH domain interacting protein (Sharpin) resulted in a severe autoinflammatory type of chronic proliferative dermatitis, inflammation in other organs, and lymphoid organ defects. To determine whether cell-type restricted loss of Sharpin causes similar lesions, a conditional null mutant was created. Ubiquitously expressing cre-recombinase recapitulated the phenotype seen in spontaneous mutant mice. Limiting expression to keratinocytes (using a Krt14-cre) induced a chronic eosinophilic dermatitis, but no inflammation in other organs or lymphoid organ defects. The dermatitis was associated with a markedly increased concentration of serum IgE and IL18. Crosses with S100a4-cre resulted in milder skin lesions and moderate to severe arthritis. This conditional null mutant will enable more detailed studies on the role of SHARPIN in regulating NFkB and inflammation, while the Krt14-Sharpin-/- provides a new model to study atopic dermatitis.
自发性突变导致 SHANK 相关 RH 结构域相互作用蛋白（Sharpin）发生严重的自身炎症性慢性增殖性皮炎、其他器官炎症和淋巴器官缺陷。为了确定细胞类型特异性 Sharpin 缺失是否会导致类似病变，创建了条件性缺失突变体。广泛表达的 cre 重组酶再现了自发突变小鼠中观察到的表型。将表达限制在角质形成细胞（使用 Krt14-cre）会诱导慢性嗜酸性粒细胞性皮炎，但其他器官无炎症或淋巴器官缺陷。这种皮炎与血清 IgE 和 IL18 浓度显著增加有关。与 S100a4-cre 的杂交导致皮肤病变较轻，关节炎从中度到重度。这种条件性缺失突变体将能够更详细地研究 SHARPIN 在调节 NFkB 和炎症中的作用，而 Krt14-Sharpin-/- 则提供了一个研究特应性皮炎的新模型。
