TABLE 1.
The genetically inactivation of PKRs in mice displayed developmental defects and organ dysfunction
| Diseases | In vivo model | Reference | |
|---|---|---|---|
| Genetically manipulated mice | |||
| Abnormal organ development | Epicardial 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 PKR2(−/−) PK2(−/−) |
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) | |
| Diabetes | Endothelial specific-PKR1(−/−) | Lipodystrophy, Insulin resistance | (Dormishian et al., 2013) |
| PKR1(−/−) (40 weeks old) | Obesity and diabetes | (Szatkowski et al., 2013) | |
| Obesity | PKR1(−/−) 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 alteration | PK2(−/−) PKR2(−/−) |
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) | |
| Pain | PK2(−/−) PKR1(−/−) |
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 infection | PKR1(−/−) PK2(−/−) |
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) |