Table 5.
Available mouse models for sirtuins research
| Sirtuin | Mouse models | Phenotypes |
|---|---|---|
| SIRT1 | KO (whole body) | In C57/B6 background, mice die within 1 month after birth. In BALB/c background or mixed background, mice can survive through adulthood with smaller body size, closed eyelids, infertility, and autoimmune-like conditions |
| KO (brain) | Memory defect, no adaptive feeding response to calorie restriction, less serum insulin-like growth factor 1 | |
| KO (liver) | Defect in circadian gene oscillation, develop hepatic steatosis and inflammation | |
| KO (macrophage) | Increased inflammation, glucose intolerance and insulin resistance induced by high fat diet | |
| Tg (whole body) | Protected against various metabolic disorders (fatty liver and type 2 diabetes) induced by high fat diet, protected against age-induced cancer, osteoporosis and glucose intolerance | |
| Tg (brain) | enhanced memory formation and feeding behavior, protected against Alzheimer’s disease | |
| Tg (heart) | Cardioprotection (mild expression), cardiac hypertrophy (high expression) | |
| Tg (gut) | Protected against colon cancer | |
| Tg (kidney) | Protected against acute renal failure | |
| SIRT2 | KO (whole body) | SiRT2 knockout female mice develop mammary tumors, whereas males develop liver and intestinal tumors |
| SIRT3 | KO (whole body) | Defect in fatty acid oxidation, cancer prone, their oocytes exhibit developmental arrest after in vitro fertilization, accumulation of hyperacetylated mitochondrial proteins, reduced respiration and adenosine triphosphate levels |
| Tg (heart) | Protected against cardiac hypertrophy | |
| SIRT4 | KO (whole body) | Developed hyperinsulinemia and lung tumors |
| SIRT5 | KO (whole body) | Defect in urea cycle, hyperammonemia after fasting |
| Tg (liver) | Increased urea cycle activity, increased urea production | |
| SIRT6 | KO (whole body) | Died around 4 weeks showing premature aging phenotype (lymphopenia, loss of subcutaneous fat), hypoglycemia, increased glucose uptake, genomic instability |
| KO (liver) | Increased glycolysis, triglyceride synthesis, reduced β oxidation and fatty liver formation | |
| Tg (whole body) | Protected against metabolic disorder induced by high fat diet | |
| SiRT7 | KO (whole body) | Died around 1 year showing premature aging phenotypes (kyphosis, loss of subcutaneous fat, degenerative cardiac hypertrophy), increased apoptosis |
Note: Adapted with permission from J Cell Sci. 2011;124(Pt 6):833–838. Nakagawa T, Guarente L. Sirtuins at a glance.259
Abbreviations: KO, knockout; Tg, transgenic.