Table 1.
Animal models with genetic variations of KLFs.
| KLF | Animal model | Phenotype |
|---|---|---|
| KLF1 | Klf1−/− | Lethal E.14, deficit in β-globin expression and erythropoiesis, severe anemia (135,136) |
| Klf1−/− & Rb+/−;Klf1+/− | Cell cycle perturbation via control of E2f2 (S-phase entry) (130,131) | |
| Klf1−/− & Klf1+/− | Transcriptional regulation of macrophage-expressed Dnase2α gene (red blood cell maturation) (138) | |
| KLF2 | Tea-TCR-Klf2 Tg | Restrainment of CD4+ cell differentiation T follicular helper (218) |
| Klf2−/− | Lethal E.12.5 – 14.5, defective blood vessel, severe bleeding (219) | |
| Splenic and lymph node T cells abnormal cell surface phenotype (220) | ||
| Embryonic globin genes expression affected, but not adult globin genes (144) | ||
| Splenomegaly, increased splenic B cell subsets (221) | ||
| Altered B-cell tissue distribution and expression of trafficking molecules (222) | ||
| Endothelial-Klf2−/− | Cardiac failure, vascular abnormalities (223) | |
| Cerebral cavernous malformations, vascular lesions, enlarged capillaries, irregular structure (224) | ||
| Glomerular endothelial cell injury, diabetic nephropathy (216) | ||
| Hematopoetic Klf2−/− | Restriction of chemokine receptor expression patterns, regulation of T-cells migration (225) | |
| T-cell-Klf2−/− | Unrestrained cytokine production, bystander chemokine receptor upregulation (226) | |
| Fetal liver Klf2−/− chimeras | Regulation of thymocyte and T-cell migration (227) | |
| Klf2−/−;APOE−/− | Increased atherosclerosis (161) | |
| Klf2/−/;Ldlr−/− | Increased atherosclerosis (162) | |
| KLF3 | Klf3−/− | Reduced adipocyte size and less white adipose tissue (87) |
| Resistance to diet-induced obesity and glucose intolerance, increased adipolin (90) | ||
| Impaired silencing of embryonic globin expression during development (139) | ||
| KLF3-H275R | Homozygotes: Lethal E.14.5–16.5 – Severe cardiac defects | |
| Heterozygotes: Perinatal death - Thick myocardial wall, enlarged chambers (228) | ||
| KLF4 | Klf4−/− | Death shortly after birth – Dehydration due to skin barrier permeability (229,230) |
| Cardiomyocyte-Klf4−/− | Mild increase of cardiac mass (153), aging-related cardiomyopathy, pressure overload cardiac hypertrophy (56) | |
| Smooth muscle-Klf4−/− | Reduced atherosclerosis lesion size, increased plaque stability and cap thickness (165) | |
| Endothelial-Klf4Tg;APOE−/− | Reduced atherosclerosis (163) | |
| Endothelial-Klf4−/−;APOE−/− | Increased atherosclerosis (163) | |
| KLF5 | Klf5−/− | Homozygotes: Lethal E.8.5 Heterozygotes: Decreased arterial-wall thickening, angiogenesis, cardiac hypertrophy, interstitial fibrosis (231) |
| Cardiac fibroblast Klf5−/− | Resistance in in pressure overload-mediated cardiac hypertrophy (154) | |
| Lung-Klf5−/− | Impaired surfactant protein and lipid production, lung structural abnormalities (232) | |
| Intestine-Klf5−/− | Altered crypt architecture and intestine morphology (233) | |
| Hematopoetic-Klf5−/− | Splenomegaly, increased peripheral white blood cells (234) | |
| Cardiomyocyte-Klf5−/− | Dilated cardiomyopathy associated with energetic deficiency (59) | |
| Klf5+/− | Lower white adipose tissue mass after birth that is abrogated later (83) | |
| Resistance to diet-induced obesity despite increased food intake (51) | ||
| KLF6 | Klf6−/− | Lethal E12.5, hematopoiesis defects (235) |
| Klf6+/− | Reduced fibrosis in response to Ang II overload (158) | |
| Cardiomyocyte-Klf6−/− | Reduced fibrosis in response to Ang II overload (158) | |
| Cardiac fibroblast-Klf6−/− | Lack of protection to Ang II-induced fibrosis (158) | |
| Hepatocyte-Klf6−/− | Reduced glucokinase and insulin sensitivity (117) | |
| Reduced hepatic PPARα protein (188) | ||
| KLF7 | Klf7−/− | Lethal within the first 3 days of life, low respiratory rate, cyanosis, defects of the olfactory and optic nerves, impaired axon growth and abnormal dendrite organization (236) |
| Neuronal Klf7 chimera | Increased neuronal regeneration capacity following axon injury (237) | |
| KLF8 | Klf8−/− | Viable but reduced life span (139) |
| KLF9 | Klf9−/− | Reduces activity in rotorod and contextual fear-conditioning tests (238) |
| KLF10 | Klf10−/− | Hyperglycemia, increased hepatic glucose production, increased plasma triglycerides, loss of circadian expression of hepatic lipid and carbohydrate metabolism genes (105) |
| Impaired insulin secretion (pancreas) (119) | ||
| KLF11 | Klf11−/− | Decreased circulating insulin, increased peripheral insulin sensitivity, dysregulation of genes involved in lipid metabolism, resistance to diet-induced obesity (126) |
| KLF12 | - | - |
| KLF13 | Klf13−/− | Splenomegaly and reduced number of circulating erythrocytes (86) |
| KLF14 | Liver-Klf14−/− | Lower plasma HDL (170) |
| KLF15 | Klf15−/− | Fasting hypoglycemia, reduced expression of hepatic and skeletal muscle catabolism genes, loss of circadian expression of hepatic metabolism genes, loss of bile acid synthetic enzymes (67,114,119,198) |
| Protection against hepatic insulin resistance and fatty liver under high-fat feeding (197) | ||
| Fatigue following endurance exercise, reduced skeletal muscle fatty acid oxidation gene expression (66) | ||
| Cardiac lipid oxidation deficit, susceptibility to pressure overload induced cardiac hypertrophy (60,155) | ||
| Adipose-KLF15 Tg | Insulin resistance and protection from weight gain, improved glucose tolerance due to increased insulin synthesis by pancreas (172) | |
| KLF16 | - | - |
| KLF17 | - | - |
| KLF18 | - | - |
| Double k/o | Klf3−/−;Klf8−/− | Lethal E14.5 (139) |