A Review of Mouse Models of Monogenic Diabetes and ER Stress Signaling.
2020
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 beta 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.
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