Table 1.

Overview of mouse models studied for proteins involved in UPR pathways and their observed phenotypes with respect to β-cell health and function.

Deletion model	Deletion Tissue	Deletion Time	Genetic Background	Phenotype	Reference
PERK	Whole body	Embryonic	129svev(Swiss Webster)	Diabetes with β-cell mass loss	Harding et al., 2001 [53]
	Pancreas		C57BL/6J or 129SvEvTac	Diabetes with impaired proliferation and differentiation of β-cells	Zhang et al., 2006 [54]
	β-cells	Adulthood	C57BL/6	Diabetes with increased β-cell death	Gao et al., 2012 [55]
ATF4	Whole body	Embryonic	C57BL/6	Protection against diet-induced obesity and diabetes	Seo et al., 2009 [60]
CHOP	Whole body	Embryonic	C57BL/6	Reduced hyperglycemia and glucose intolerance on high-fat diet	Song et al., 2008 [61]
			db/db	Increased obesity, normal glucose tolerance due to β-cell mass expansion
			Akita	Delayed diabetes onset	Oyadomari et al., 2002 [77]
			NOD	No effect on diabetes incidence, delayed appearance of insulin autoantibodies	Satoh et al., 2011 [95]
	β-cells	Adulthood	C57BL/6J	Alleviates ER stress and protects from hepatic steatosis	Yong et al., 2021 [62]
p58	Whole body	Embryonic	C57BL/6J	Hyperglycemia with β-cell death	Ladiges et al., 2005 [59]
IRE1α	β-cells	Embryonic	C57BL/6J	Impaired insulin secretion with no apparent change in islet morphology or mass	Xu et al., 2014 [64]
		Adulthood	C57BL/6	Diabetes, defects in secretion of proinsulin, increased oxidative stress	Hassler et al., 2015 [65]
		Postnatal	NOD	Transient hyperglycemia followed by protection from diabetes	Lee et al., 2020 [90]
GRP78	β-cells	Embryonic	N/A	Insulin-deficient diabetes, impaired β-cell differentiation	Sharma et al., 2018 [72]
XBP1	β-cells	Embryonic	C57BL/6	Hyperglycemia, glucose intolerance, decreased insulin secretion	Lee et al., 2011 [63]
ATF6α	Whole body	Embryonic	C57BL/6	Hyperglycemia on high-fat diet	Usui et al., 2012 [68]
			Agouti	Hyperglycemia, improved insulin sensitivity on high-fat diet
			Akita
	β-cells	Postnatal	C57BL/6	Loss of protective effects of TUDCA against diabetes, mild glucose intolerance	Engin et al., 2013 [69]