B6.Cg-Col1a1^{tm1(CAG-Sirt1)Dsin}/Mmjax

Stock number: 010771
Research areas: Neurobiology Research, Research Tools

Description

The SIRT1^STOP (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 SIRT1^STOP (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.

Detailed description

Mice homozygous for this SIRT1^STOP (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 SIRT1^STOP (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.

Development

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 SIRT1^STOP 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.

Allele

Symbol: Col1a1^{tm1(CAG-Sirt1)Dsin}
Name: targeted mutation 1, David Sinclair
MGI accession ID: MGI:4430570
Generation method: Targeted
Attributes: Conditional ready (e.g. floxed); Inserted expressed sequence
Marker symbol: Col1a1
Marker name: collagen, type I, alpha 1
Chromosome: 11
Strain of origin: (C57BL/6 x 129S4/SvJae)F1
Expressed genes: Sirt1,sirtuin 1,mouse, laboratory
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.