Establishment of a Mouse Model for Porokeratosis Due to Mevalonate Diphosphate Decarboxylase Deficiency.

IF 2 4区医学 Q3 DERMATOLOGY

Skin Research and Technology Pub Date : 2024-09-01 DOI:10.1111/srt.70076

Kexin Peng, Wenghong Wong, Qiaoan Zhang, Yumeng La, Zhen Tian, Ruilin Sun, Loksi Ho, Kaihang Yang, Jiewen Pan, Jing Luan, Zhenmin Niu, Zhenghua Zhang

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引用次数: 0

Abstract

Introduction: Porokeratosis (PK) is an autoinflammatory keratinization disease (AIKD) characterized by circular or annular skin lesions with a hyperkeratotic rim, pathologically shown as the cornoid lamella. Four genes that cause PK are associated with the mevalonate (MV) pathway. In Chinese PK patients, mevalonate diphosphate decarboxylase (MVD) is the most common causative gene. The lack of an animal model has greatly limited research on PK pathogenesis.

Materials and methods: In this research, we constructed K14-CreER^T2-Mvd^fl/fl mice using the Cre-LoxP system to create a mouse model for in-depth studies of PK. The Epidermal Mvd gene was knocked out by intraperitoneal injection of Tamoxifen (TAM). Pathology, immunohistochemistry, RNA-seq, and Western Blot analysis were performed.

Results: Skin lesions appeared following Mvd deficiency, and pathological examination revealed the characteristic cornoid lamella, as well as cutaneous inflammation. Furthermore, we observed elevated levels of IL-17A and IL-1β, and a decreased Loricrin level in epidermal Mvd-deficient mice. Compared with the wild-type (WT) group, Mvd deficiency activated the expression of lipid metabolism-related proteins.

Conclusion: We developed the first mouse model for PK research, enabling further studies on disease development and treatment approaches.

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建立因甲羟戊酸二磷酸脱羧酶缺乏而导致角化病的小鼠模型

导言：角化病（Porokeratosis，PK）是一种自身炎症性角质化疾病（AIKD），其特征是圆形或环形皮肤病变，边缘角化过度，病理上表现为角质层。导致 PK 的四个基因与甲羟戊酸（MV）途径有关。在中国的 PK 患者中，甲羟戊酸二磷酸脱羧酶（MVD）是最常见的致病基因。缺乏动物模型极大地限制了对PK发病机制的研究：在本研究中，我们利用Cre-LoxP系统构建了K14-CreERT2-Mvdfl/fl小鼠，为深入研究PK建立了一个小鼠模型。通过腹腔注射他莫昔芬（TAM）敲除表皮Mvd基因。研究人员对小鼠进行了病理学、免疫组织化学、RNA-seq和Western Blot分析：结果：Mvd缺乏后出现皮肤病变，病理检查发现了特征性的粟粒状薄片以及皮肤炎症。此外，我们还观察到表皮 Mvd 缺乏的小鼠 IL-17A 和 IL-1β 水平升高，Loricrin 水平降低。与野生型（WT）组相比，Mvd缺陷激活了脂质代谢相关蛋白的表达：我们建立了第一个用于 PK 研究的小鼠模型，有助于进一步研究疾病的发展和治疗方法。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Skin Research and Technology 医学-皮肤病学

CiteScore

3.30

自引率

9.10%

发文量

审稿时长

6-12 weeks

期刊介绍： Skin Research and Technology is a clinically-oriented journal on biophysical methods and imaging techniques and how they are used in dermatology, cosmetology and plastic surgery for noninvasive quantification of skin structure and functions. Papers are invited on the development and validation of methods and their application in the characterization of diseased, abnormal and normal skin. Topics include blood flow, colorimetry, thermography, evaporimetry, epidermal humidity, desquamation, profilometry, skin mechanics, epiluminiscence microscopy, high-frequency ultrasonography, confocal microscopy, digital imaging, image analysis and computerized evaluation and magnetic resonance. Noninvasive biochemical methods (such as lipids, keratin and tissue water) and the instrumental evaluation of cytological and histological samples are also covered. The journal has a wide scope and aims to link scientists, clinical researchers and technicians through original articles, communications, editorials and commentaries, letters, reviews, announcements and news. Contributions should be clear, experimentally sound and novel.