Table 1

Animal Models With Genetic Variations of KLFs

Animal ModelPhenotype (Ref. #)
KLF1Klf1–/–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)
KLF2Tea-TCR-Klf2 TgRestrainment 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–/– chimerasRegulation of thymocyte and T-cell migration (226)
Klf2–/–; APOE–/–Increased atherosclerosis (161)
Klf2/–/; Ldlr–/–Increased atherosclerosis (162)
KLF3Klf3–/–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-H275RHomozygotes: Lethal E14.5–16.5, severe cardiac defects
Heterozygotes: Perinatal death, thick myocardial wall, enlarged chambers (227)
KLF4Klf4–/–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)
KLF5Klf5–/–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)
KLF6Klf6–/–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)
KLF7Klf7–/–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 chimeraIncreased neuronal regeneration capacity after axon injury (236)
KLF8Klf8–/–Viable but reduced lifespan (139)
KLF9Klf9–/–Reduces activity in rotarod and contextual fear–conditioning tests (237)
KLF10Klf10–/–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)
KLF11Klf11–/–Decreased circulating insulin, increased peripheral insulin sensitivity, dysregulation of genes involved in lipid metabolism, resistance to diet-induced obesity (126)
KLF12
KLF13Klf13–/–Splenomegaly and reduced number of circulating erythrocytes (86)
KLF14Liver-Klf14–/–Lower plasma HDL level (169)
KLF15Klf15–/–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 TgInsulin resistance and protection from weight gain, improved glucose tolerance due to increased insulin synthesis by pancreas (171)
KLF16
KLF17
KLF18
Double k/oKlf3–/–; 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.