The SIRT1STOP (or SIRT1-Tg flox-STOP-flox) targeted allele has a floxed-STOP cassette and mouse sirtuin 1 (Sirt1) cDNA sequence inserted into the 3' UTR of the collagen A1 (Col1a1) locus. When bred to mice that express Cre recombinase, offspring will have the floxed-STOP cassette deleted in the cre-expressing tissue(s), resulting in Sirt1 overexpression in Col1a1-expressing cells. These SIRT1STOP (or SIRT1-Tg flox-STOP-flox) mice may be useful for generating conditional mutations for studying the role of sirtuin NAD+-deacetylases in aging, cancer, cellular stress resistance, genomic stability, IGF1 pathways, autoimmunity, inflammation, T cell tolerance, energy metabolism, neurodegeneration, insulin resistance, and diabetes.
David A Sinclair, Harvard Medical School
Genetic Background | Generation |
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Allele Type | Gene Symbol | Gene Name |
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Targeted (Conditional ready (e.g. floxed), Inserted expressed sequence) | Col1a1 | collagen, type I, alpha 1 |
Mice homozygous for this SIRT1STOP (or SIRT1-Tg flox-STOP-flox) targeted allele are viable and fertile, with a floxed-STOP cassette and mouse sirtuin 1 (Sirt1) cDNA sequence inserted into the 3' UTR of the collagen A1 (Col1a1) locus. When bred to mice that express Cre recombinase, offspring will have the floxed-STOP cassette deleted in the cre-expressing tissue(s), resulting in Sirt1 overexpression in Col1a1-expressing cells. These SIRT1STOP (or SIRT1-Tg flox-STOP-flox) mice may be useful for generating conditional mutations for studying the role of sirtuin NAD+-deacetylases in aging, cancer, cellular stress resistance, genomic stability, IGF1 pathways, autoimmunity, inflammation, T cell tolerance, energy metabolism, neurodegeneration, insulin resistance, and diabetes.
The SIRT1-Tg flox-STOP-flox construct was designed to insert (from 5' to 3') an FRT site, a CMV-IE enhancer/chicken beta-actin/rabbit beta-globin hybrid promoter (CAG; from the pCAGGS vector), a loxP-flanked transcriptional STOP cassette, the mouse sirtuin 1 (Sirt1) cDNA sequence, and a PGK-hygro-polyA sequence (with a second FRT site between the PGK and hygro) into the 3' UTR of the mouse collagen A1 (Col1a1) locus. The targeting vector was electroporated into (C57BL/6 x 129S4Sv/Jae)F1-derived V6.5 embryonic stem (ES) cells. Correctly targeted ES cells were injected into recipient blastocysts, and chimeric males were bred with C57BL/6J females to generate the colony. These SIRT1STOP mice were backcrossed to C57BL/6J mice for 12 generations prior to arrival at The Jackson Laboratory. Upon arrival, mutant mice were bred to C57BL/6J inbred mice to establish the colony.
Expressed Gene | Sirt1, sirtuin 1, mouse, laboratory |
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Site of Expression |
Allele Name | targeted mutation 1, David Sinclair |
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Allele Type | Targeted (Conditional ready (e.g. floxed), Inserted expressed sequence) |
Allele Synonym(s) | Col1a1Sirt1-Tg flox-STOP-flox; ColA1flox-STOP-Sirt1; SIRT1STOP |
Gene Symbol and Name | Col1a1, collagen, type I, alpha 1 |
Gene Synonym(s) | |
Promoter | CAG, CMV-IE enhancer/chicken beta-actin/rabbit beta-globin hybrid promoter, |
Expressed Gene | Sirt1, sirtuin 1, mouse, laboratory |
Strain of Origin | (C57BL/6 x 129S4/SvJae)F1 |
Chromosome | 11 |
Molecular Note | The SIRT1-Tg flox-STOP-flox construct was designed to insert (from 5' to 3') an FRT site, a CMV-IE enhancer/chicken beta-actin/rabbit beta-globin hybrid promoter (CAG; from the pCAGGS vector), a loxP-flanked transcriptional STOP cassette, the mouse sirtuin 1 (Sirt1) cDNA sequence, and a PGK-hygro-polyA sequence (with a second FRT site between the PGK and hygro) into the 3' UTR of the mouse collagen A1 (Col1a1) locus. |
Mutations Made By | David Sinclair, Harvard Medical School |
When maintaining a live colony, homozygous mice may be bred together.
When using the B6.Cg-Col1a1tm1(CAG-Sirt1)Dsin/Mmjax mouse strain in a publication, please cite the originating article(s) and include MMRRC stock #32033 in your Materials and Methods section.
Facility Barrier Level Descriptions
The Jackson Laboratory has rigorous genetic quality control and mutant gene genotyping programs to ensure the genetic background of JAX® Mice strains as well as the genotypes of strains with identified molecular mutations. JAX® Mice strains are only made available to researchers after meeting our standards. However, the phenotype of each strain may not be fully characterized and/or captured in the strain data sheets. Therefore, we cannot guarantee a strain's phenotype will meet all expectations. To ensure that JAX® Mice will meet the needs of individual research projects or when requesting a strain that is new to your research, we suggest ordering and performing tests on a small number of mice to determine suitability for your particular project. We do not guarantee breeding performance and therefore suggest that investigators order more than one breeding pair to avoid delays in their research.
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