UOC Reumatologia e Malattie Autoinfiammatorie, IRCCS Istituto Giannina Gaslini, Genoa, Italy.
Genetica Medica, IRCCS Istituto Giannina Gaslini, Genoa, Italy.
Methods Mol Biol. 2023;2696:281-297. doi: 10.1007/978-1-0716-3350-2_19.
Autoinflammatory diseases are a group of distinct disorders characterized by recurrent fever and inflammatory manifestations predominantly mediated by cytokines of the innate immune system, particularly IL-1β, without involvement of autoantibodies or autoreactive T lymphocytes. Cryopyrin-associated periodic syndromes (CAPS), due to NLRP3 gene mutations, represent the prototype of these diseases. Owing to their genetic nature, most of these disorders have an early onset, ranging from the first hours to the first decade of life. Due to the rarity of CAPS patients and to the limitations of working with pediatric samples, the development of animal models of this disease is of great help for studying both pathophysiology and therapeutic strategies. In this chapter, we review the generation and characterization of a knock-in mouse bearing the NLRP3 gene with the N475K mutation, associated with CINCA, the most severe form of human CAPS.
自身炎症性疾病是一组以反复发热和炎症表现为特征的疾病，主要由先天免疫系统细胞因子介导，特别是白细胞介素-1β，不涉及自身抗体或自身反应性 T 淋巴细胞。由于 NLRP3 基因突变引起的 cryopyrin 相关周期性综合征（CAPS）是这些疾病的典型代表。由于其遗传性质，这些疾病大多数在生命的前几个小时到第一个十年内发病。由于 CAPS 患者的罕见性以及儿科样本处理的局限性，该疾病的动物模型的开发对于研究其病理生理学和治疗策略非常有帮助。在本章中，我们回顾了一种带有 NLRP3 基因 N475K 突变的基因敲入小鼠的产生和特征，该突变与 CINCA 相关，CINCA 是人类 CAPS 中最严重的形式。
