Sirt1super mice have a threefold increase in SIRT1 expression directed by its endogenous promoter/enhancer regions on a BAC transgene. They may be useful when studying telomere deacetylation, DNA repair, energy homeostasis.
Manuel Serrano, Spanish National Cancer Research Centre (CNIO)
Mice homozygous for the Sirt1super BAC are viable and fertile. These mice express a wild-type mouse sirtuin 1 (Sirt1) gene directed by its endogenous promoter/enhancer regions on the BAC transgene. The donating investigator reports that genomic construct also contains the adjacent DnaJ (Hsp40) homolog, subfamily C, member 12 (Dnajc12) gene, but notes the absence of effect of DNAJC12 inhibition on the molecular pathways affected by SIRT1. SIRT1 is a protein deacetylase involved with telomere deacetylation, DNA repair, energy homeostasis. As such SIRT1 plays roles in telomere length maintenance, tumor growth, and improved metabolic syndrome caused by high fat diets. Sirt1super mice exhibit a threefold increase in SIRT1 expression in liver, brown adipose tissue, and muscle. On a high fat diet they show lower lipid induced inflammation, increased glucose tolerance, and are almost entirely protected from hepatic steatosis, although, they gain fat mass similar to wild-type mice. Sirt1super mice are protected from liver cancer promoted by high-fat diet,
but are prone to thyroid and prostate cancer in combination with Pten-deficiency. Sirt1super mice have a normal longevity but some aging-associated phenotypes are improved.
Bacterial artificial chromosome (BAC) library (CHORI) was used to obtain a 174 kb BAC (#RP23-119G23) containing the entire mouse Sirt1 (sirtuin 1) gene. This BAC was microinjected into fertilized (C57BL6 x CBA)F1 oocytes and founder mice, carrying one copy of the BAC, were bred to C57BL/6J.OlaHsd inbred mice for at least 5 generations. Upon arrival at The Jackson Laboratory, mice were bred to C57BL/6J inbred mice (Stock No. 000664) for at least one generation to establish the colony.
|Expressed Gene||Sirt1, sirtuin 1, mouse, laboratory|
|Site of Expression|
|Allele Name||transgene insertion A, Manuel Serrano|
|Allele Type||Transgenic (Inserted expressed sequence)|
|Allele Synonym(s)||SIRT1super; Sirt1-tg|
|Gene Symbol and Name||Tg(Sirt1)ASrn, transgene insertion A, Manuel Serrano|
|Promoter||Sirt1, sirtuin 1, mouse, laboratory|
|Expressed Gene||Sirt1, sirtuin 1, mouse, laboratory|
|Strain of Origin||(C57BL/6 x CBA)F1|
|Molecular Note||Bacterial artificial chromosome (BAC) library (CHORI) was used to obtain a 174 kb BAC (#RP23-119G23) containing the entire mouse Sirt1 gene and the adjacent Dnajc12 gene. Overexpression of Dnajc12 is not expected to affect Sirt1 molecular pathways. The one founder mouse created exhibits a 2-4 fold overexpression of SIRT1 protein in liver, kidney, thymus, spleen, colon and jejunum/ileum.|
When maintaining a live colony homozygous mice may be bred together.
When using the Sirt1super mouse strain in a publication, please cite the originating article(s) and include JAX stock #024510 in your Materials and Methods section.
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