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斑秃的C3H/HeJ小鼠和DEBR大鼠模型:临床前药物筛选方法及结果综述

The C3H/HeJ mouse and DEBR rat models for alopecia areata: review of preclinical drug screening approaches and results.

作者信息

Sun Jing, Silva Kathleen A, McElwee Kevin J, King Lloyd E, Sundberg John P

机构信息

The Jackson Laboratory, Bar Harbor, ME 04609-1500, USA.

出版信息

Exp Dermatol. 2008 Oct;17(10):793-805. doi: 10.1111/j.1600-0625.2008.00773.x.

Abstract

The C3H/HeJ inbred mouse strain and the Dundee Experimental Bald Rat (DEBR) strain spontaneously develop adult onset alopecia areata (AA), a cell-mediated disease directed against actively growing hair follicles. The low frequency of AA and the inability to predict the stage of AA as it evolves in the naturally occuring C3H/HeJ model of AA can be converted into a highly predictable system by grafting full thickness skin from AA-affected mice to normal haired mice of the same strain. The rat DEBR model develops spontaneous AA at a higher frequency than in the mouse model but they are more expensive to use in drug studies owing to their larger size. Regardless of the shortcomings of either model, these rodent models can be used succesfully to screen novel or approved drugs for efficacy to treat human AA. As the pathogenesis of AA follows the canonical lymphocytic co-stimulatory cascade in the mouse AA model, it can be used to screen compounds potentially useful to treat a variety of cell-mediated diseases. Efficacy of various agents can easily be screened by simply observing the presence, rate, and cosmetic acceptability of hair regrowth. More sophisticated assays can refine how the drugs induce hair regrowth and evaluate the underlying pathogenesis of AA. Some drugs commonly used to treat human AA patients work equally as well in both rodent models validating their usefulness as models for drug efficacy and safety for humanAA.

摘要

C3H/HeJ近交系小鼠和邓迪实验性秃头大鼠(DEBR)品系会自发发生成年期斑秃(AA),这是一种针对活跃生长毛囊的细胞介导疾病。在AA的自然发生的C3H/HeJ模型中,AA的低发生率以及无法预测AA发展阶段的情况,可以通过将受AA影响小鼠的全层皮肤移植到同品系的正常毛发小鼠身上,转化为一个高度可预测的系统。大鼠DEBR模型比小鼠模型更易自发发生AA,但由于其体型较大,在药物研究中的使用成本更高。尽管这两种模型都有缺点,但这些啮齿动物模型可成功用于筛选新型或已获批药物治疗人类AA的疗效。由于AA的发病机制在小鼠AA模型中遵循典型的淋巴细胞共刺激级联反应,因此它可用于筛选可能对治疗多种细胞介导疾病有用的化合物。通过简单观察毛发再生的存在、速度和美容可接受性,就能轻松筛选各种药物的疗效。更复杂的检测方法可以细化药物诱导毛发再生的方式,并评估AA的潜在发病机制。一些常用于治疗人类AA患者的药物在两种啮齿动物模型中效果相同,这验证了它们作为人类AA药物疗效和安全性模型的有用性。

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