Université Libre de Bruxelles, Bruxelles, Belgium.
Methods Mol Biol. 2020;2128:55-67. doi: 10.1007/978-1-0716-0385-7_4.
Diabetes is a major public health problem: it is estimated that 420 million people are affected globally. Monogenic forms of diabetes are less common, but variants in monogenic diabetes genes have been shown to contribute to type 2 diabetes risk. In vitro and in vivo models of monogenic forms of diabetes related to the endoplasmic reticulum (ER) stress response provided compelling evidence on the role of ER stress and dysregulated ER stress signaling on β cell demise in type 1 and type 2 diabetes. In this chapter, we describe the genetics, background, and phenotype of ER stress-related monogenic diabetes mouse models, and we comment on their advantages and disadvantages. We conclude that these mouse models are very useful tools for monogenic diabetes molecular pathogenesis studies, although there is a variability on the methodology that is used. Regarding the use of these models for therapeutic testing of ER stress modulators, a specific consideration should be given to the fact that they recapitulate some, but not all, the phenotypic characteristics of the human disease.
据估计，全球有 4.2 亿人受到影响。单基因形式的糖尿病比较少见，但单基因糖尿病基因的变异已被证明与 2 型糖尿病的风险有关。与内质网（ER）应激反应有关的单基因糖尿病的体外和体内模型提供了令人信服的证据，证明 ER 应激和 ER 应激信号的失调在 1 型和 2 型糖尿病中对β细胞死亡起作用。在这一章中，我们描述了与 ER 应激相关的单基因糖尿病小鼠模型的遗传学、背景和表型，并对它们的优缺点进行了评论。我们得出的结论是，这些小鼠模型是研究单基因糖尿病分子发病机制的非常有用的工具，尽管在使用的方法上存在一定的差异。关于将这些模型用于 ER 应激调节剂的治疗性测试，应特别考虑到它们再现了人类疾病的一些但不是所有表型特征这一事实。
