National and Kapodistrian University of Athens, School of Health Sciences, Department of Pharmacy, Section of Pharmaceutical Technology, Panepistimiopolis, 15784 Athens, Greece.
Pathologoanatomic Laboratory, Athens Naval Hospital, 11521 Athens, Greece.
J Pharmacol Toxicol Methods. 2021 Mar-Apr;108:107054. doi: 10.1016/j.vascn.2021.107054. Epub 2021 Mar 26.
Psoriasis, is a common, chronic, autoimmune, inflammatory, relapsing disease, which would benefit from reliable and human-relevant animal models to test drugs pre-clinically and to understand their mechanism of action. Because of its ease of use, convenience and low cost, the imiquimod (IMQ)-induced psoriasis-like model is widely utilized; however, it is not known whether all mouse strains are equivalent and if the hairless mouse is appropriate, so that the imiquimod model can be further optimized.
Under similar experimental conditions, common mouse strains (BALB/c, C57BL/6J, and ApoE) and a new hairless strain (ApoE/SKH-hr2) as well as several inducers (IMQ, IMQ + acetic acid (AcOH) topical and IMQ + AcOH systemic) were compared by clinical, histopathological, biophysical and locomotor activity assessments.
The BALB/c mice yielded an optimal psoriasis-like phenotype with IMQ + AcOH topical treatment, and the corresponding phenotypes for the other mouse strains were C57BL/6J moderate and ApoE mild. In contrast, the ApoE/SKH-hr2 mice, as a result of the absence of a Munro abscess in the histopathology analysis, left doubt about the psoriasis-like acquisition. Locomotor activity of BALB/c mice treated with IMQ, IMQ + AcOH topically and IMQ + AcOH systemically showed decreased distance and rearing coverage and increased immobility with all treatments. Hence, the BALB/c mouse strain appears to be an optimal psoriasis-like model when utilizing IMQ + AcOH topical application.
银屑病是一种常见的慢性自身免疫性炎症性疾病,需要可靠且与人类相关的动物模型来进行临床前药物测试,并了解其作用机制。由于咪喹莫特(IMQ)诱导的银屑病样模型具有使用方便、成本低等优点,因此被广泛应用;然而,目前尚不清楚所有小鼠品系是否等效,以及无毛小鼠是否合适,因此需要进一步优化 IMQ 模型。
在相似的实验条件下,通过临床、组织病理学、生物物理和运动活性评估,比较了普通小鼠品系(BALB/c、C57BL/6J 和 ApoE)和一种新的无毛品系(ApoE/SKH-hr2)以及几种诱导剂(IMQ、IMQ+乙酸(AcOH)局部和 IMQ+AcOH 全身)。
BALB/c 小鼠经 IMQ+AcOH 局部处理后表现出最佳的银屑病样表型,而其他小鼠品系的表型为 C57BL/6J 中度和 ApoE 轻度。相比之下,由于组织病理学分析中缺乏 Munro 脓肿,ApoE/SKH-hr2 小鼠对银屑病样获得产生了怀疑。经 IMQ、IMQ+AcOH 局部和 IMQ+AcOH 全身处理的 BALB/c 小鼠的运动活性显示,所有处理均导致距离和后肢伸展减少,静止时间增加。因此,当使用 IMQ+AcOH 局部应用时,BALB/c 小鼠品系似乎是一种最佳的银屑病样模型。