Table 1.
Animal Models With Genetic Variations of KLFs
| Animal Model | Phenotype (Ref. #) | |
|---|---|---|
| KLF1 | Klf1–/– | Lethal E14, deficit in β-globin expression and erythropoiesis, severe anemia 135, 136 |
| Klf1–/– and Rb+/-;Klf1+/– | Cell cycle perturbation via control of E2f2 (S-phase entry) 130, 131 | |
| Klf1–/– and 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 (217) |
| Klf2–/– | Lethal E12.5–14.5, defective blood vessel, severe bleeding (218) | |
| Splenic and lymph node T cells, abnormal cell surface phenotype (219) | ||
| Embryonic globin genes expression affected but not adult globin genes (144) | ||
| Splenomegaly, increased splenic B-cell subsets (220) | ||
| Altered B-cell tissue distribution and expression of trafficking molecules (221) | ||
| Endothelial-Klf2–/– | Cardiac failure, vascular abnormalities (222) | |
| Cerebral cavernous malformations, vascular lesions, enlarged capillaries, irregular structure (223) | ||
| Glomerular endothelial cell injury, diabetic nephropathy (215) | ||
| Hematopoietic Klf2–/– | Restriction of chemokine receptor expression patterns, regulation of T-cell migration (224) | |
| T-cell-Klf2–/– | Unrestrained cytokine production, bystander chemokine receptor upregulation (225) | |
| Fetal liver Klf2–/– chimeras | Regulation of thymocyte and T-cell migration (226) | |
| 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 E14.5–16.5, severe cardiac defects Heterozygotes: Perinatal death, thick myocardial wall, enlarged chambers (227) |
|
| KLF4 | Klf4–/– | Death shortly after birth, dehydration due to skin barrier permeability 228, 229 |
| 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 E8.5 Heterozygotes: Decreased arteria wall thickening, angiogenesis, cardiac hypertrophy, interstitial fibrosis (230) |
| Cardiac fibroblast Klf5–/– | Resistance in pressure overload–mediated cardiac hypertrophy (154) | |
| Lung-Klf5–/– | Impaired surfactant protein and lipid production, lung structural abnormalities (231) | |
| Intestine-Klf5–/– | Altered crypt architecture and intestine morphology (232) | |
| Hematopoetic-Klf5–/– | Splenomegaly, increased peripheral white blood cells (233) | |
| 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 (234) |
| 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 (187) | ||
| 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 (235) |
| Neuronal Klf7 chimera | Increased neuronal regeneration capacity after axon injury (236) | |
| KLF8 | Klf8–/– | Viable but reduced lifespan (139) |
| KLF9 | Klf9–/– | Reduces activity in rotarod and contextual fear–conditioning tests (237) |
| 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 level (169) |
| 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, 197 |
| Protection against hepatic insulin resistance and fatty liver under high-fat feeding (196) | ||
| Fatigue after 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 (171) | |
| KLF16 | — | — |
| KLF17 | — | — |
| KLF18 | — | — |
| Double k/o | Klf3–/–; Klf8–/– | Lethal E14.5 (139) |
Ang = angiotensin; APOE = apolipoprotein E; CD = cluster of differentiation; E = embryonic day; HDL = high-density lipoprotein; KLF = Krüppel-like factor; k/o = knockout; PPAR = peroxisome proliferator activated receptor; Tg = transgenic.