Table 2. Phenotypes of conditional IRS knockout and Foxo knockout mice using the Cre-LoxP genetic approaches.
| Tissue-specific IRS or Foxo null mice genotype | Phenotype | Cre- mice | Ref. |
|---|---|---|---|
| Hypothalamic & β-cell IRS2-/- | Obesity; hyperglycemia; insulin resistance | Rip-cre | Lin X |
| Hypothalamic (AGRP neuron) Foxo1-/- | Leanness, reduced food intake; increase insulin and leptin sensitivity | Agrp-cre | Ren H |
| Hypothalamic (POMC neuron) Foxo1-/- | Leanness, reduced food intake; increase insulin and leptin sensitivity | Pomc-cre | Plum L |
| Leptin receptor neuron IRS2-/- | Obesity; hyperglycemia; insulin resistance | Lep-R-cre | Sadagur |
| Leptin receptor neuron Foxo1-/-∷IRS2-/- | Leanness; protect obesity and hyperglycemia from IRS2 deficiency | Lep-R-cre | Sadagur |
| Liver IRS1-/- | Normal glucose; severe insulin resistance on high-fat diet | Alb-cre | Guo S |
| Liver IRS2-/- | Normal glucose | Alb-cre | Guo S |
| Liver IRS1-/-∷IRS2-/- | Hyperglycemia; insulin resistance | Alb-cre | Guo S Kubota |
| Liver Foxo1-/- | Reduced blood glucose | Alb-cre | Zhang K |
| Liver Foxo3-/- | Normal glucose | Alb-cre | Zhang K |
| Liver Foxo4-/- | Normal glucose | Alb-cre | Zhang K |
| Liver Foxo1-/-∷ Foxo3-/-∷ Foxo4-/- | Reduced blood glucose; increased triglycerides and hepatic steatosis | Alb-cre | Zhang K Haeusler |
| Liver Foxo1-/-∷ IRS1/-∷ IRS2-/- | Protect hyperglycemia from hepatic IRS1 and IRS2 deficiency | Alb-cre | Dong X |
| Skeletal&Cardiac muscle IRS1-/-∷IRS2-/- | Normal glucose; normal insulin; die 2 weeks after birth | MCK-cre | Long Y |
| Cardiac IRS1-/-∷IRS2-/- | Male die of heart failure at the age of 7 weeks; hyperlipidemia | αMhc-cre | Qi Y |
| Cardiac Foxo1-/- | Prevent heart failure from high-fat diet | αMhc-cre | Battipr K |
| Cardiac Foxo3-/- | No prevent heart failure from high-fat diet | αMhc-cre | Battipr K |
| Pancreatic β-cell Foxo1-/- | Reduced β-cell regeneration; β-cell dedifferentiated into progenitor-like cells or α-cells; hyperglucagonemia; hyperglycemia | Ins2-cre | Talchaic |
| Endothelium IRS1-/-∷IRS2-/- | Reduced Akt and eNOS phosphorylation; impaired skeletal muscle glucose uptake and insulin resistance | Tie2-cre | Kubota T |
| Endothelium Foxo1-/-∷Foxo3-/-∷Foxo4-/- | Increased eNOS phosphorylation; reduced inflammation and oxidative stress of endothelium; prevented atherosclerosis | Tie2-cre | Tsuchiya |
| Bone osteoblasts Foxo1-/- | Increased osteocalcin and insulin production; reduced blood glucose concentration | Collagen I-cre | Rached |
Abbreviation of promoters driving cre expression: RIP- rat insulin promoter; Agrp- agouti-regulated peptide; Pomc- pro-opiomelanocortin; Lep R- leptin receptor; Alb- albumin; MCK- muscle creatine kinase; αMHC- myosin heavy chain α; Ins2- insulin 2; Tie2- Angiopoietin 2 receptor.