Overview

This SIRT1-KI mutant mouse strain may be useful in studies of metabolic homeostasis, physical performance and aging and lifespan.

Donating Investigator

Leonard P Guarente, Massachusetts Institute of Technology

Genetic overview

Genetic Background	Generation

Actb^{tm3.1(Sirt1)Npa}

Allele Type	Gene Symbol	Gene Name
Targeted (Inserted expressed sequence)	Actb	actin, beta

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Research Applications

Developmental Biology Research
Cell Biology Research
Internal/Organ Research
Endocrine Deficiency Research
Reproductive Biology Research
Research Tools
Diabetes and Obesity Research
Cardiovascular Research

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Base Price

Starting at:

$2,854.50 Domestic price Cryo Recovery

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Details

Detailed Description

Mice that are heterozygous for the targeted mutation are viable, exhibit delayed reproduction and lower body weight. No homozygotes are produced from heterozygous crosses. Fewer than expected heterozygotes are produced from heterozygote X wildtype crosses. Overexpression of gene product (protein) is detected by Western blot analysis of white adipose tissue, brown adipose tissue, MEFs, skull calvaria cells and brain tissue. Overexpression of the protein is not detected in liver or muscle tissue. Fusion gene product (mRNA) is detected in white adipose tissue by Northern blot analysis. Beta-actin protein expression is equivalent to wildtype levels. Heterozygote knock-in mice have reduced fat mass (epididymal fat pad weight), circulating free fatty acids, leptin, adiponectin and total cholesterol. Food consumption, glucose tolerance and metabolic rate (with associated higher oxygen consumption) are increased in the mutant mice. In fasted conditions, heterozygotes have lower circulating glucose levels than controls. In fed condition, heterozygotes have lower circulating insulin levels than controls.

Development

A targeting vector containing mouse SIRT1 cDNA, bovine growth hormone polyadenylation sequence, IRES sequence and floxed neo cassette was inserted into the 3' untranslated region of the mouse beta-actin locus. The construct was electroporated into C57BL/6J derived embryonic stem (ES) cells. Correctly targeted ES cells were injected into recipient blastocysts. The resulting chimeric animals were crossed to mice expressing Cre recombinase (on the C57BL/6 background) to excise the floxed neo selection cassette. The Donating Investigator backcrossed the mice to C57BL/6 (see SNP note below) for many generations.
Upon arrival at The Jackson Laboratory, the mice were crossed to C57BL/6J (Stock No. 000664) at least once to establish the colony.

A 32 SNP (single nucleotide polymorphism) panel analysis, with 27 markers covering all 19 chromosomes and the X chromosome, as well as 5 markers that distinguish between the C57BL/6J and C57BL/6N substrains, was performed on the rederived living colony at The Jackson Laboratory Repository. While the 27 markers throughout the genome suggested a C57BL/6 genetic background, 3 of 5 markers that determine C57BL/6J from C57BL/6N were found to be segregating. These data suggest the mice sent to The Jackson Laboratory Repository were on a mixed C57BL/6J ; C57BL/6N genetic background.

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

Bordone L; Cohen D; Robinson A; Motta MC; van Veen E; Czopik A; Steele AD; Crowe H; Marmor S; Luo J; Gu W; Guarente L. 2007. SIRT1 transgenic mice show phenotypes resembling calorie restriction. Aging Cell 6(6):759-67PubMed: 17877786 MGI: J:160212

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Genetics

Actb^{tm3.1(Sirt1)Npa}

Allele Symbol: Actb^{tm3.1(Sirt1)Npa}

Allele Name	targeted mutation 3.1, Novartis Pharma AG
Allele Type	Targeted (Inserted expressed sequence)
Allele Synonym(s)	SIRT1-KI⁺
Gene Symbol and Name	Actb, actin, beta
Gene Synonym(s)
Expressed Gene	Sirt1, sirtuin 1, mouse, laboratory
Strain of Origin	C57BL/6J
Chromosome	5
Molecular Note	The 3' UTR was replaced with a cassette containing an IRES sequence, floxed neo cassette, mouse Sirt1 cDNA, and a bovine growth hormone polyadenylation sequence. Cre mediated recombination removed the neo cassette. Western blot analysis confirmed expression of the cDNA in white adipose tissue, brown adipose tissue, brain, calvaria cells of the skull, and mouse embryonic fibroblasts but not in the liver or muscle. Normal expression of Actb was confirmed by western blot analysis.

Disease/Phenotype

Disease Terms

Research Areas By Phenotype

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

Developmental Biology Research
- Embryonic Lethality (Homozygous)
- Growth Defects
Cell Biology Research
- Genes Regulating Growth and Proliferation
Internal/Organ Research
- Adipose Defects
Endocrine Deficiency Research
- Adipose Defects
Reproductive Biology Research
- Fertility Defects
Research Tools
- Reproductive Biology Research
- Metabolism Research
Diabetes and Obesity Research
- Hypoinsulinemia
Cardiovascular Research
- Hypocholesterolemia

Mammalian Phenotype Terms by Genotype

The following phenotype information is associated with a similar, but not exact match to this JAX^® Mice strain

Genotype: Actb^{tm3.1(Sirt1)Npa}/Actb⁺
involves: 129/Sv * C57BL/6 * C57BL/6J

adipose tissue phenotype

decreased epididymal fat pad weight
- at 3 months

homeostasis/metabolism phenotype

decreased circulating leptin level
- at 3 and 12 months

decreased circulating LDL cholesterol level

decreased fasting circulating glucose level
- reduced plasma glucose levels in fasted mice at 6 months of age

improved glucose tolerance

decreased circulating adiponectin level
- at 12 months

decreased circulating cholesterol level
- at 3 and 12 months

increased oxygen consumption
- at 7 months of age

decreased circulating HDL cholesterol level

decreased circulating free fatty acids level
- at 12 months

decreased circulating insulin level
- in fed mice at 6 months of age

mammalian phenotype

behavior/neurological phenotype
- Normal - mice exhibit normal baseline physical activity

homeostasis/metabolism phenotype
- Normal - mice exhibit normal levels of circulating triglyceride, glycerol, IGF, IGF-1, lactate, hydrobutyrate, and corticosterone

mortality/aging

preweaning lethality, incomplete penetrance
- fewer than expected mice are produced (no time of death given)

reproductive system phenotype

delayed fertility

behavior/neurological phenotype

increased food intake
- increase in food consumption normalized to body weight

abnormal motor coordination/balance
- mice exhibit improved performance on a rotarod compared with wild-type mice

growth/size/body region phenotype

decreased body weight

Genotype: Actb^{tm3.1(Sirt1)Npa}/Actb^{tm3.1(Sirt1)Npa}
involves: 129/Sv * C57BL/6 * C57BL/6J

mortality/aging

preweaning lethality, complete penetrance
- no mice are produced (no time of death given)

References

Bordone L; Cohen D; Robinson A; Motta MC; van Veen E; Czopik A; Steele AD; Crowe H; Marmor S; Luo J; Gu W; Guarente L. 2007. SIRT1 transgenic mice show phenotypes resembling calorie restriction. Aging Cell 6(6):759-67PubMed: 17877786 MGI: J:160212

Additional - Actb^{tm3.1(Sirt1)Npa} related

Technical Support

CONTACT TECHNICAL SUPPORT

Genotyping Protocols
- Standard PCR:Actb
- Standard PCR:Actb
- Genotyping resources and troubleshooting
Breeding Considerations

When maintaining a live colony, these mice can be bred as heterozygotes. No homozygotes are produced from heterozygous crosses. Fewer than expected heterozygotes are produced from heterozygote X wildtype crosses. Heterozygous mice exhibit delayed reproduction.
- Additional Breeding and Husbandry Support
Citation
When using the C57BL/6-Actb^{tm3.1(Sirt1)Npa}/J mouse strain in a publication, please cite the originating article(s) and include JAX stock #013080 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

Pricing & Availability

Cryo Recovery

Domestic
International

Live Mouse

Age

Genotype

Price

weeks

Cryorecovery - Pricing

Service/Product	Description	Price
> >	Heterozygous or wildtype for Actb<tm3.1(Sirt1)Npa>

Related Products and Services

Frozen Mouse Embryo	C57BL/6-Actb<tm3.1(Sirt1)Npa>/J	$2595.00
Frozen Mouse Embryo	C57BL/6-Actb<tm3.1(Sirt1)Npa>/J	$2595.00
Frozen Mouse Embryo	C57BL/6-Actb<tm3.1(Sirt1)Npa>/J	$3373.50
Frozen Mouse Embryo	C57BL/6-Actb<tm3.1(Sirt1)Npa>/J	$3373.50

Payment Terms and Conditions

Terms are granted by individual review and stated on the customer invoice(s) and account statement. These transactions are payable in U.S. currency within the granted terms. Payment for services, products, shipping containers, and shipping costs that are rendered are expected within the payment terms indicated on the invoice or stated by contract. Invoices and account balances in arrears of stated terms may result in The Jackson Laboratory pursuing collection activities including but not limited to outside agencies and court filings.

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

Questions about Terms of Use

Additional Use Restrictions Apply

Use of MICE by companies or for-profit entities requires a license prior to shipping.

Licensing Information

Phone: 207-288-6470

Email: TechTran@jax.org

Donating Investigator

Genetic overview

Research Applications

Base Price

Detailed Description

Development

Expression Data

Control Suggestions

Additional Information

Selected References

Actbtm3.1(Sirt1)Npa

Allele Symbol: Actbtm3.1(Sirt1)Npa

Disease Terms

Research Areas By Phenotype

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

Mammalian Phenotype Terms by Genotype

Genotype: Actbtm3.1(Sirt1)Npa/Actb+involves: 129/Sv * C57BL/6 * C57BL/6J

adipose tissue phenotype

homeostasis/metabolism phenotype

mammalian phenotype

mortality/aging

reproductive system phenotype

behavior/neurological phenotype

growth/size/body region phenotype

Genotype: Actbtm3.1(Sirt1)Npa/Actbtm3.1(Sirt1)Npainvolves: 129/Sv * C57BL/6 * C57BL/6J

mortality/aging

References

Additional - Actbtm3.1(Sirt1)Npa related

Genotyping Protocols

Breeding Considerations

Citation

Animal Health Reports

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

Live Mouse

Cryorecovery - Pricing

Related Products and Services

Payment Terms and Conditions

The Jackson Laboratory's Genotype Promise

Terms Of Use

Additional Use Restrictions Apply

Licensing Information

Actb^{tm3.1(Sirt1)Npa}

Allele Symbol: Actb^{tm3.1(Sirt1)Npa}

Genotype: Actb^{tm3.1(Sirt1)Npa}/Actb⁺
involves: 129/Sv * C57BL/6 * C57BL/6J

Genotype: Actb^{tm3.1(Sirt1)Npa}/Actb^{tm3.1(Sirt1)Npa}
involves: 129/Sv * C57BL/6 * C57BL/6J

Additional - Actb^{tm3.1(Sirt1)Npa} related