Sirtuins - colloquially known as the longevity genes – are a highly conserved family of NAD1+-dependent enzymes which are involved in the regulation of gene silencing, metabolism, cell division, apoptosis, and genetic material repair. Additionally, it has been reported that sirtuins play important roles in the development of multi-systemic diseases.
There are seven sirtuin homologs in mammals (SIRT1 to SIRT7) that share a conserved NAD+ binding domain, but differ among their cellular localization and functional activities. SIRT1, SIRT6, and SIRT7 predominantly localize to the nucleus (SIRT7 primarily resides in nucleolus). SIRT2 localizes to the cytoplasm, while SIRT3, SIRT4, and SIRT5 localize to the mitochondria. Sirtuins mediate various cellular functions, including cell cycle control, balancing mitochondrial dynamics, autophagy, and cell growth.
For many years, Sirtuin (SIRT) genetic knockout (KO) mouse models have been used to advance studies across a wide range of scientific disciplines. The following is a brief summary about mammalian sirtuins, SIRT1 to SIRT7, and their respective KO mouse model applications.
| Sirtuin Homologs | Phenotypic Variation | Applications | Subcellular Compartments |
|---|---|---|---|
| SIRT1 | Most mice die perinatally; retinal, bone, and cardiac defects observed. | Limited (constitutive KO not recommended) | Nucleus (predominant), cytoplasm |
| SIRT2 | No significant phenotypic abnormalities. | Cell cycle, tumorigenesis, neurodegeneration, metabolism, and inflammatory response | Cytoplasm (predominant), nucleus |
| SIRT3 |
Developmentally normal; changes in AceCS2 activity, ATP levels, and mitochondrial protein acetylation. |
Metabolic regulation, studies of mammalian mitochondrial acetyl-coA synthetase (AceCS2) | Mitochondria |
| SIRT4 | Increased mitochondrial activity of glutamate dehydrogenase (GDH). | Insulin secretion studies | Mitochondria |
| SIRT5 | Defect in regulation of the urea cycle. | Ammonia detoxification and mitochondrial metabolism research | Mitochondria |
| SIRT6 | Progeroid syndrome; profound hypoglycemia, death at four weeks. | Limited (constitutive KO not recommended) | Nucleus |
| SIRT7 | Reduced lifespan, cardiomyopathy. | Limited (constitutive KO not recommended) | Nucleus (nucleolus) |
Cyagen AI Knockout Mouse Model eBank offers over 16,000 strains of ready-to-use knockout (KO) / conditional knockout (cKO) mouse models, including Sirt2, Sirt3, Sirt4, and Sirt5 live KO mice. Search our updated catalog now for your gene(s) of interest – our database will automatically provide you with a personalized contact form if you would like to inquire about a specific gene KO.
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References:
Finkel, T., Deng, C. & Mostoslavsky, R. Recent progress in the biology and physiology of sirtuins. Nature 460, 587–591 (2009). https://doi.org/10.1038/nature08197
Ye X., Li M., Hou T., Gao T., Zhu W., Yang Y. Sirtuins in glucose and lipid metabolism. Oncotarget. 2016; 8: 1845-1859. Retrieved from https://www.oncotarget.com/article/12157/text/
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