Strain Name:

B6.129-Sirt2tm1.1Fwa/J

Stock Number:

012772

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Availability:

Repository- Live

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Sirt2tm1.1Fwa mice exhibit genomic instability and chromosomal aberrations, and are prone to tumorigenesis. These mice may be useful in studies of necroptosis and tumorigenesis.

Description

Strain Information

Former Names B6.129-Sirt2tm1Fwa/J    (Changed: 28-APR-10 )
Type Congenic; Mutant Strain; Targeted Mutation;
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Mating SystemHomozygote x Homozygote         (Female x Male)   07-JAN-11
Specieslaboratory mouse
GenerationN9+F2 (30-JUN-11)
Generation Definitions
 
Donating InvestigatorDr. Frederick W. Alt,   Children's Hospital

Description
Loss of SIRT2 is associated with greater genome instability in that SIRT2 depletion significantly reduces PR-Set7 chromatin levels, alters the size and number of PR-Set7 foci, and decreases the overall mitotic deposition of histone H4 (H4K16Ac), an epigenetic mark that has been proposed to directly regulate chromatin. Sirt2tm1.1Fwa mice are also prone to tumorigenesis. Mice from this strain have been used to study the role of sirtuin 2 (silent mating type information regulation 2, homolog) 2 in programmed necrosis (necroptosis), which may have important implications in the cellular response to a host of insults, including bacterial and viral infection, various neurodegenerative processes, as well as ischaemia-reperfusion injury of the brain and heart.

Development
A targeting vector was designed to replace exon 5-6 and part of exon 7 of the mouse sirtuin (silent information regulator 2 (Sir2)) homolog 2, Sirt2 gene with a floxed neomycin (neo)-resistance cassette. This construct was electroporated into 129S6/SvEvTac-derived TC1 embryonic stem (ES) cells. Correctly targeted ES cells were transiently transfected with a cre expression plasmid for the purpose of removing the neo cassette. ES cells that had successfully undergone Cre-mediated recombination and no longer retained the cassette were injected into C57BL/6J blastocysts and the resulting chimeric males were bred to 129/Sv females. These mice were then backcrossed to C57BL/6 for 8 generations to produce homozygous Sirt2-/- mice. Upon arrival at The Jackson Laboratory, mice were bred to C57BL/6J (Stock No. 000664) for at least one generation to establish the colony.

Control Information

  Control
   000664 C57BL/6J (approximate)
 
  Considerations for Choosing Controls

Phenotype

Phenotype Information

View Mammalian Phenotype Terms

Mammalian Phenotype Terms provided by MGI
      assigned by genotype

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

Sirt2tm1.1Fwa/Sirt2tm1.1Fwa

        involves: 129S6/SvEvTac * C57BL/6
  • cellular phenotype
  • abnormal apoptosis
    • cells exposed to oxidative stress progress rapidly through G1 where apoptosis occurs   (MGI Ref ID J:195041)
  • abnormal cell cycle
    • H2O2 treated fibroblasts are not blocked at G2/M as in controls   (MGI Ref ID J:195041)
    • increased number of cells passing through G2/M   (MGI Ref ID J:195041)
    • more fibroblasts in G1 phase and fewer in S phase   (MGI Ref ID J:195041)
    • delayed entry into S phase but faster progress through S   (MGI Ref ID J:195041)
    • abnormal mitosis
      • oxidative stress leads to increased mitosis   (MGI Ref ID J:195041)
  • abnormal chromosome morphology
    • increased chromosome re-replication, more cells that are greater than 4n   (MGI Ref ID J:195041)
    • increased number of double strand DNA breaks, particularly in S phase cells   (MGI Ref ID J:195041)
    • increased chromosomal aberrations   (MGI Ref ID J:195041)
  • tumorigenesis
  • altered tumor susceptibility
    • increased susceptibility to skin tumors (papillomas) when treated with DMBA followed by 15 weeks of TPA application to skin   (MGI Ref ID J:195041)
    • tumors by week 8 of treatment   (MGI Ref ID J:195041)
    • 50% mortality by week 35   (MGI Ref ID J:195041)
    • no spontaneous tumors   (MGI Ref ID J:195041)
  • mortality/aging
  • increased sensitivity to xenobiotic induced morbidity/mortality
    • 50% mortality after beginning treatment with DMBA followed by 15 weeks of TPA application to skin   (MGI Ref ID J:195041)
  • homeostasis/metabolism phenotype
  • increased sensitivity to xenobiotic induced morbidity/mortality
    • 50% mortality after beginning treatment with DMBA followed by 15 weeks of TPA application to skin   (MGI Ref ID J:195041)
View Research Applications

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

Metabolism Research

Genes & Alleles

Gene & Allele Information provided by MGI

 
Allele Symbol Sirt2tm1.1Fwa
Allele Name targeted mutation 1.1, Frederick W Alt
Allele Type Targeted (Null/Knockout)
Mutation Made ByDr. Frederick Alt,   Children's Hospital
Strain of Origin129S6/SvEvTac
Gene Symbol and Name Sirt2, sirtuin 2
Chromosome 7
Gene Common Name(s) 5730427M03Rik; RIKEN cDNA 5730427M03 gene; SIR2; SIR2L; SIR2L2; Sir2l; silent mating type information regulation 2, (S.cerevisiae, homolog)-like;
Molecular Note A targeting vector was designed to replace exon 5-6 and part of exon 7 with a floxed PGK-neomycin (neo)-resistance cassette. Cre-mediated recombination removed the neo cassette. [MGI Ref ID J:177028] [MGI Ref ID J:195041]

Genotyping

Genotyping Information

Genotyping Protocols

Sirt2tm1.1Fwa, Standard PCR


Helpful Links

Genotyping resources and troubleshooting

References

References provided by MGI

Additional References

Sirt2tm1.1Fwa related

Alt FW. 2011. Direct Data Submission MGI Direct Data Submission :.  [MGI Ref ID J:177028]

Lin J; Sun B; Jiang C; Hong H; Zheng Y. 2013. Sirt2 suppresses inflammatory responses in collagen-induced arthritis. Biochem Biophys Res Commun 441(4):897-903. [PubMed: 24211200]  [MGI Ref ID J:211504]

North BJ; Rosenberg MA; Jeganathan KB; Hafner AV; Michan S; Dai J; Baker DJ; Cen Y; Wu LE; Sauve AA; van Deursen JM; Rosenzweig A; Sinclair DA. 2014. SIRT2 induces the checkpoint kinase BubR1 to increase lifespan. EMBO J 33(13):1438-53. [PubMed: 24825348]  [MGI Ref ID J:211655]

Pais TF; Szego EM; Marques O; Miller-Fleming L; Antas P; Guerreiro P; de Oliveira RM; Kasapoglu B; Outeiro TF. 2013. The NAD-dependent deacetylase sirtuin 2 is a suppressor of microglial activation and brain inflammation. EMBO J 32(19):2603-16. [PubMed: 24013120]  [MGI Ref ID J:202478]

Rothgiesser KM; Erener S; Waibel S; Luscher B; Hottiger MO. 2010. SIRT2 regulates NF-kappaB dependent gene expression through deacetylation of p65 Lys310. J Cell Sci 123(Pt 24):4251-8. [PubMed: 21081649]  [MGI Ref ID J:182906]

Serrano L; Martinez-Redondo P; Marazuela-Duque A; Vazquez BN; Dooley SJ; Voigt P; Beck DB; Kane-Goldsmith N; Tong Q; Rabanal RM; Fondevila D; Munoz P; Kruger M; Tischfield JA; Vaquero A. 2013. The tumor suppressor SirT2 regulates cell cycle progression and genome stability by modulating the mitotic deposition of H4K20 methylation. Genes Dev 27(6):639-53. [PubMed: 23468428]  [MGI Ref ID J:195041]

Wang YP; Zhou LS; Zhao YZ; Wang SW; Chen LL; Liu LX; Ling ZQ; Hu FJ; Sun YP; Zhang JY; Yang C; Yang Y; Xiong Y; Guan KL; Ye D. 2014. Regulation of G6PD acetylation by SIRT2 and KAT9 modulates NADPH homeostasis and cell survival during oxidative stress. EMBO J 33(12):1304-20. [PubMed: 24769394]  [MGI Ref ID J:211669]

Health & husbandry

Health & Colony Maintenance Information

Animal Health Reports

Room Number           AX10

Colony Maintenance

Breeding & HusbandryWhen maintaining a live colony, homozygous mice may be bred.
Mating SystemHomozygote x Homozygote         (Female x Male)   07-JAN-11
Diet Information LabDiet® 5K52/5K67

Pricing and Purchasing

Pricing, Supply Level & Notes, Controls


Pricing for USA, Canada and Mexico shipping destinations View International Pricing

Live Mice

Price per mouse (US dollars $)GenderGenotypes Provided
Individual Mouse $199.90Female or MaleHomozygous for Sirt2tm1.1Fwa  
Price per Pair (US dollars $)Pair Genotype
$399.80Homozygous for Sirt2tm1.1Fwa x Homozygous for Sirt2tm1.1Fwa  

Standard Supply

Repository-Live.
Repository-Live represents an exclusive set of over 1800 unique mouse models across a vast array of research areas. Breeding colonies provide mice for large and small orders and fluctuate in size depending on current research demand. If a strain is not immediately available, you will receive an estimated availability timeframe for your inquiry or order in 2-3 business days. Repository strains typically are delivered at 4 to 8 weeks of age. Requests for specific ages will be noted but not guaranteed and we do not accept age requests for breeder pairs. However, if cohorts of mice (5 or more of one gender) are needed at a specific age range for experiments, we will do our best to accommodate your age request.

Pricing for International shipping destinations View USA Canada and Mexico Pricing

Live Mice

Price per mouse (US dollars $)GenderGenotypes Provided
Individual Mouse $259.90Female or MaleHomozygous for Sirt2tm1.1Fwa  
Price per Pair (US dollars $)Pair Genotype
$519.80Homozygous for Sirt2tm1.1Fwa x Homozygous for Sirt2tm1.1Fwa  

Standard Supply

Repository-Live.
Repository-Live represents an exclusive set of over 1800 unique mouse models across a vast array of research areas. Breeding colonies provide mice for large and small orders and fluctuate in size depending on current research demand. If a strain is not immediately available, you will receive an estimated availability timeframe for your inquiry or order in 2-3 business days. Repository strains typically are delivered at 4 to 8 weeks of age. Requests for specific ages will be noted but not guaranteed and we do not accept age requests for breeder pairs. However, if cohorts of mice (5 or more of one gender) are needed at a specific age range for experiments, we will do our best to accommodate your age request.

View USA Canada and Mexico Pricing View International Pricing

Standard Supply

Repository-Live.
Repository-Live represents an exclusive set of over 1800 unique mouse models across a vast array of research areas. Breeding colonies provide mice for large and small orders and fluctuate in size depending on current research demand. If a strain is not immediately available, you will receive an estimated availability timeframe for your inquiry or order in 2-3 business days. Repository strains typically are delivered at 4 to 8 weeks of age. Requests for specific ages will be noted but not guaranteed and we do not accept age requests for breeder pairs. However, if cohorts of mice (5 or more of one gender) are needed at a specific age range for experiments, we will do our best to accommodate your age request.

Control Information

  Control
   000664 C57BL/6J (approximate)
 
  Considerations for Choosing Controls
  Control Pricing Information for Genetically Engineered Mutant Strains.
 

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