The genetically inactivation of PKRs in mice displayed developmental defects and organ dysfunction

DiseasesIn vivo modelReference
Genetically manipulated mice
Abnormal organ developmentEpicardial specific PKR1(−/−)Embryonic lethality due to impaired heart development(Arora et al., 2016a)
Nephron specific PKR1(−/−)Impaired nephrogenesis and glomerulogenesis(Arora et al., 2016b)
PKR1(−/−)Dilated cardiomyopathy and vascular rarefaction, macrophage infiltration, lipotoxicity, fibrosis in heart(Boulberdaa et al., 2011)
PKR2(−/−)OB hypoplasia, severe atrophy of the reproductive system, including the testis, ovary, uterus, vagina, and mammary glands, defective migration and differentiation of neuronal progenitors(Matsumoto et al., 2006; Prosser et al., 2007)
PK2(−/−)Small OB, and the accumulation of neuronal progenitors in the RMS,
disrupted GnRH neuron migration, hypogonadotropic hypogonadism
(Ng et al., 2005; Pitteloud et al., 2007)
PKR2LacZ/+ and
PK2EGFP mice
Tangential and radial migration defects of neuroblasts in the SVZ-RMS-OB resulting in loss of ∼75% of GABAergic interneurons in the OB(Wen et al., 2019)
Cardiovascular diseases (CVDs)Endothelial specific-PKR1(−/−)Dilated cardiomyopathy and vascular rarefaction(Dormishian et al., 2013)
Cardiac fibroblast progenitor-specific PKR1(−/−)Vascular rarefaction and development of Epicardial adipose tissue(Qureshi et al., 2017)
TG-PKR2 (PKR2 overexpression in cardiomyocytes)Hypertrophic cardiomyopathy with endotheliopathy(Urayama et al., 2009)
TG-PKR1 (PKR1 overexpression in cardiomyocytes)Neovasculogenesis, activation of epicardial progenitor cells(Urayama et al., 2008)
DiabetesEndothelial specific-PKR1(−/−)Lipodystrophy, Insulin resistance(Dormishian et al., 2013)
PKR1(−/−) (40 weeks old)Obesity and diabetes(Szatkowski et al., 2013)
ObesityPKR1(−/−) and PKR2(−/−)PK2 via PKR1 reduces food intake and body weight in a mouse model of human obesity.(Beale et al., 2013)
PKR1(−/−) (40 weeks old)Obesity and diabetes,
Adipogenesis, infiltration of macrophage into fat tissue
(Szatkowski et al., 2013)
PK2(−/−)Absence of the fasting-induced arousal, and d less energy expenditure, torpor after fasting(Zhou et al., 2012)
PKR2(−/−)Hypothalamic regulation of energy balance, fasting induced hypothermia and torpor(Jethwa et al., 2008)
Adipocyte specific-PKR1(−/−)Obesity, accumulation of fat tissue, increase adipogenesis(Szatkowski et al., 2013)
Circadian cycle alterationPK2(−/−)
Significantly reduced rhythmicity for sleep-wake cycle, body temperature, as well as the expression of peripheral clock genes, precision in timing the onset of nocturnal locomotor activity(Li et al., 2006; Hu et al., 2007; Prosser et al., 2007; Jethwa et al., 2008)
TG-PK2 (PK2 overexpression)Reduced oscillation of PK2 mRNA levels in the SCN and decreased amplitude of behavioral rhythm(Li et al., 2018)
Attenuated thermal and noxious chemical stimuli-mediated nociception in -PK2(−/−)
Impaired nociception and inflammatory pain sensation in PKR1(−/−)
(Martucci et al., 2006; Negri et al., 2006a; Franchi et al., 2008)
PKR2(−/−)Reduced nociceptive sensitivity to the noxious cold temperature of 4°C and hot temperatures of 46°C and 48°C in the workingrange(Maftei et al., 2020)
PKR1(−/−) and PKR2(−/−)Less inflammation-induced hyperalgesia(Giannini et al., 2009)
PK2(−/−)Strong reduction in nociception induced by thermal and chemical stimuli, capsaicin, but no difference in inflammatory response to capsaicin(Hu et al., 2006)
Inflammation and infectionPKR1(−/−)
Loss of macrophage migration, proinflammatory phenotype,
(T-helper1 cytokines (IL-2, IL-1beta) in PKR1(−/−)
Low survival rate of sepsis in PK2(−/−) mice
(Martucci et al., 2006; Franchi et al., 2008; Yu et al., 2022)