Overview

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.

Donating Investigator

David A Sinclair, Harvard Medical School

Genetic overview

Genetic Background	Generation

Col1a1^{tm1(CAG-Sirt1)Dsin}

Allele Type	Gene Symbol	Gene Name
Targeted (Conditional ready (e.g. floxed), Inserted expressed sequence)	Col1a1	collagen, type I, alpha 1

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Research Applications

Research Tools
Neurobiology Research

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Details

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.

Expression Data

Expressed Gene	Sirt1, sirtuin 1, mouse, laboratory
Site of Expression

Control Suggestions

000664 C57BL/6J

Additional Information

Considerations for Choosing Controls

Selected References

Firestein R; Blander G; Michan S; Oberdoerffer P; Ogino S; Campbell J; Bhimavarapu A; Luikenhuis S; de Cabo R; Fuchs C; Hahn WC; Guarente LP; Sinclair DA. 2008. The SIRT1 deacetylase suppresses intestinal tumorigenesis and colon cancer growth. PLoS One 3(4):e2020PubMed: 18414679 MGI: J:134301

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Genetics

Col1a1^{tm1(CAG-Sirt1)Dsin}

Allele Symbol: Col1a1^{tm1(CAG-Sirt1)Dsin}

Allele Name	targeted mutation 1, David Sinclair
Allele Type	Targeted (Conditional ready (e.g. floxed), Inserted expressed sequence)
Allele Synonym(s)	Col1a1^{Sirt1-Tg flox-STOP-flox}; ColA1^{flox-STOP-Sirt1}; SIRT1^STOP
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

Disease/Phenotype

Disease Terms

Research Areas By Phenotype

This mouse can be used to support research in many areas including:

Research Tools
- Genetics Research
  - Mutagenesis and Transgenesis
  - Tissue/Cell Markers
  - Mutagenesis and Transgenesis: Cre-lox System
  - Tissue/Cell Markers: Cre-lox System
- Diabetes and Obesity Research
  - loxP
- Reproductive Biology Research
  - Cre-lox System
- Cre-lox System
  - loxP-flanked Sequences: Test/Reporter
  - loxP-flanked Sequences
- Cardiovascular Research
  - Cre-lox System
- Developmental Biology Research
  - Cre-lox System
Neurobiology Research
- Cre-lox System
  - loxP-flanked Sequences: Test/Reporter
  - loxP-flanked Sequences

Mammalian Phenotype Terms by Genotype

References

Firestein R; Blander G; Michan S; Oberdoerffer P; Ogino S; Campbell J; Bhimavarapu A; Luikenhuis S; de Cabo R; Fuchs C; Hahn WC; Guarente LP; Sinclair DA. 2008. The SIRT1 deacetylase suppresses intestinal tumorigenesis and colon cancer growth. PLoS One 3(4):e2020PubMed: 18414679 MGI: J:134301

Additional - Col1a1^{tm1(CAG-Sirt1)Dsin} related

Technical Support

CONTACT TECHNICAL SUPPORT

Genotyping Protocols
- Genotyping resources and troubleshooting
Breeding Considerations

When maintaining a live colony, homozygous mice may be bred together.
- Additional Breeding and Husbandry Support
Citation
When using the B6.Cg-Col1a1^{tm1(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.

Animal Health Reports

Facility Barrier Level Descriptions

Production of mice from cryopreserved embryos or sperm occurs in a maximum barrier room, G200

The Jackson Laboratory's Genotype Promise

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.

Terms Of Use

General Terms and Conditions

See MMRRC for Additional Conditions of Distribution

Questions about Terms of Use

Licensing Information

Phone: 207-288-6470

Email: TechTran@jax.org

Donating Investigator

Genetic overview

Research Applications

Detailed Description

Development

Expression Data

Control Suggestions

Additional Information

Selected References

Col1a1tm1(CAG-Sirt1)Dsin

Allele Symbol: Col1a1tm1(CAG-Sirt1)Dsin

Disease Terms

Research Areas By Phenotype

This mouse can be used to support research in many areas including:

Mammalian Phenotype Terms by Genotype

References

Additional - Col1a1tm1(CAG-Sirt1)Dsin related

Genotyping Protocols

Breeding Considerations

Citation

Animal Health Reports

Production of mice from cryopreserved embryos or sperm occurs in a maximum barrier room, G200

The Jackson Laboratory's Genotype Promise

Terms Of Use

Licensing Information

Col1a1^{tm1(CAG-Sirt1)Dsin}

Allele Symbol: Col1a1^{tm1(CAG-Sirt1)Dsin}

Additional - Col1a1^{tm1(CAG-Sirt1)Dsin} related