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Strain Name:

129-Sirt6tm1Fwa/J

Stock Number:

006050

Availability:

Repository- Live

Price and Supply Information

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Additional Licensing and Use Restrictions

Genes & Alleles   Sirt6;   Sirt6tm1Fwa;

Product Information

Strain Details

Type JAX® GEMM® Strain - Mutant Stock
Additional information on JAX® GEMM® Strains.
Type JAX® GEMM® Strain - Targeted Mutation
Specieslaboratory mouse
Donating Investigator Frederick Alt,   Children's Hospital
Generation?+F3 (01-MAY-08)

Strain Description
Homozygous neonates are smaller than their wildtype and heterozygous littermates. They develop normally until approximately 21 days of age, when they develop an acute and rapid, aging-like degenerative pathology resulting in death by postnatal day 24. Homozygous mutant mice exhibit subcutaneous fat loss, lordokyphosis (hunchbacked spine) with osteopenia (30% loss of bone mineral density), colitis, and severe lymphopenia due to increased lymphocyte apoptosis. At day 12, mice have reduced insulin-like growth factor I (IGF-1) levels in serum, and develop severe hypoglycemia. Mouse embryonic fibroblasts (MEFs) prepared from homozygous embryos exhibit reduced proliferation, defective base excision repair function, as indicated by increased sensitivity to alkylating agents and ionizing radiation, and increased chromosomal aberrations. The donating investigators report that no gene product (mRNA or protein) is detected by RT-PCR or immuoblot analysis of tissues, MEFs or embryonic stem cells from homozygotes. The targeting construct placed a lacZ expression cassette in frame into exon 1 of the mRNA coding sequence, and beta-galactosidase staining is detected in most adult and embryonic tissues. This mutant mouse strain may be useful in studies related to DNA damage repair, genomic stability, and aging.

Strain Development
A targeting vector containing the lacZ and neomycin resistance genes was used to disrupt exons 1 to 6. The construct was electroporated into 129S6/SvEvTac-derived TC1 embryonic stem (ES) cells. Correctly targeted ES cells were injected into C57BL/6J blastocysts. The resulting chimeric male animals were crossed to 129X1/SvJ female mice.

Mammalian Phenotype Terms assigned by genotype

Sirt6tm1Fwa/Sirt6tm1Fwa

        involves: 129X1/SvJ
  • lethality-postnatal
  • lethality at weaning (MGI Ref ID J:112817)
    • fail to thrive and die around P24
  • cellular phenotype
  • decreased cell proliferation (MGI Ref ID J:112817)
    • in MEFs and ES cells
  • increased cellular sensitivity to alkylating agents (MGI Ref ID J:112817)
    • increased sensitivity of MEFs to monofunctional alkylating agents suggesting a defect in base excision repair; however double strand break repair and nucleotide excision repair are similar to wild type
  • increased cellular sensitivity to ionizing radiation (MGI Ref ID J:112817)
    • increased DNA damage and reduced survival in MEFs and ES cells following exposure to ionizing radiation; however, UV sensitivity of MEFs is similar to wild type cells
    • thymocytes from 21 day old mice display increased sensitivity to IR and monofunctional alkylating agents; however sensitivity of cells from 12 day old mice is similar to wild type
  • spontaneous chromosome breakage (MGI Ref ID J:112817)
    • increase in the frequency of fragmented chromosome, detached centromeres and chromosomal gaps in metaphase spreads from early and late passage MEFs
    • spectral karyotype analysis detects increases in the frequency of chromosome breaks, translocations, and dicentric chromosomes
  • growth/size phenotype
  • decreased body size (MGI Ref ID J:112817)
    • significantly smaller by about 10 days of age
  • postnatal growth retardation (MGI Ref ID J:112817)
    • similar size at birth but significantly smaller by about 10 days of age; however food intake is normal
  • adipose tissue phenotype
  • decreased subcutaneous adipose tissue amount (MGI Ref ID J:112817)
    • acute loss beginning around 3 weeks of age
  • digestive/alimentary phenotype
  • colitis (MGI Ref ID J:112817)
    • consisting of erosion of the superficial colonic epithelium beginning around 3 weeks of age
  • hematopoietic system phenotype
  • abnormal lymphopoiesis (MGI Ref ID J:112817)
    • 10-fold reduction in the number of splenic lymphoctes
    • abnormal B cell differentiation (MGI Ref ID J:112817)
      • 10-fold reduction in the number of B cell progenitors in the bone marrow
    • decreased double-positive T cell number (MGI Ref ID J:112817)
      • 50-fold reduction in the thymus
  • abnormal spleen cellularity (MGI Ref ID J:112817)
    • 10-fold reduction in the number of splenic lymphoctes
  • decreased bone marrow cell number (MGI Ref ID J:112817)
    • 10-fold reduction in the number of B cell progenitors in the bone marrow
  • decreased leukocyte cell number (MGI Ref ID J:112817)
    • severe lymphopenia associated with increased lymphocyte apoptosis
    • adoptive transfer studies indicate increased lymphocyte apoptosis is not a cell intrinsic defect
    • decreased double-positive T cell number (MGI Ref ID J:112817)
      • 50-fold reduction in the thymus
  • homeostasis/metabolism phenotype
  • decreased circulating glucose level (MGI Ref ID J:112817)
    • decreases rapidly in mice older than 12 days of age, dropping below detection limits by 24 days of age
  • decreased circulating insulin-like growth factor I level (MGI Ref ID J:112817)
    • serum levels of insulin like growth factor (IGF1) are low at 12 days of age and severely by 19 days of age
  • skeleton phenotype
  • decreased bone density (MGI Ref ID J:112817)
    • 30% reduction in bone mineral density at about 3 weeks of age
  • kyphosis (MGI Ref ID J:112817)
    • lordokyphosis visible around 3 weeks of age
  • lordosis (MGI Ref ID J:112817)
    • lordokyphosis visible around 3 weeks of age
  • immune system phenotype
  • abnormal lymphopoiesis (MGI Ref ID J:112817)
    • 10-fold reduction in the number of splenic lymphoctes
    • abnormal B cell differentiation (MGI Ref ID J:112817)
      • 10-fold reduction in the number of B cell progenitors in the bone marrow
    • decreased double-positive T cell number (MGI Ref ID J:112817)
      • 50-fold reduction in the thymus
  • abnormal spleen cellularity (MGI Ref ID J:112817)
    • 10-fold reduction in the number of splenic lymphoctes
  • colitis (MGI Ref ID J:112817)
    • consisting of erosion of the superficial colonic epithelium beginning around 3 weeks of age
  • decreased leukocyte cell number (MGI Ref ID J:112817)
    • severe lymphopenia associated with increased lymphocyte apoptosis
    • adoptive transfer studies indicate increased lymphocyte apoptosis is not a cell intrinsic defect
    • decreased double-positive T cell number (MGI Ref ID J:112817)
      • 50-fold reduction in the thymus

Gene & Allele Details

Allele Symbol Sirt6tm1Fwa
Allele Name targeted mutation 1, Frederick W Alt
Site of ExpressionExpression of lacZ can be detected in most adult and embryonic tissues.
Gene Symbol and Name Sirt6, sirtuin 6 (silent mating type information regulation 2, homolog) 6 (S. cerevisiae)
Chromosome 10
Gene Common Name(s) 2810449N18Rik; AI043036; RIKEN cDNA 2810449N18 gene; SIR2L6; expressed sequence AI043036;
General Note Phenotypic Similarity to Human Syndrome: Progeria
Molecular Note A LacZ gene was inserted in frame after the first 21 bp of exon 1 via homologous recombination replacing exons 1 to 6. [MGI Ref ID J:112817]

Control Information

  Control
   Wild-type from the colony
 
  Considerations for Choosing Controls
  Control Pricing Information for JAX® GEMM® Strains

Genotyping Protocols

Sirt6tm1Fwa

Colony Maintenance

Breeding & HusbandryWhen maintaining a live colony, these mice are bred as heterozygotes. Mice homozygous for the mutation do not survive past postnatal day 24
Diet Information LabDiet® 5K52/5K67

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002292   129-Gt(ROSA)26Sor/J
003451   129-Smad3tm1Par/J
003310   129S-Gt(ROSA)26Sortm1Sor/J
003383   129S-Nogtm1Amc/J
004545   129S-Npytm1Rpa/J
005091   129S-Pnpla6tm1Blw/J
007199   129S-Sgpl1Gt(ROSA)78Sor/J
003082   129S1/SvImJ-Bcl2tm1Mpin/J
004178   B6.129(Cg)-Tg(CAG-Bgeo/GFP)21Lbe/J
004478   B6.129-Foxd1tm1Lai/J
006939   B6.129-Fut1tm1Sdo/J
005768   B6.129-Htr5atm1Dgen/J
002938   B6.129-Kdrtm1Jrt/J
004158   B6.129-Maftm1Gsb/J
006497   B6.129-Skiltm2Spw/J
005772   B6.129P2-Acvrl1tm1Dgen/J
006431   B6.129P2-Adam21tm1Dgen/J
005770   B6.129P2-Adamts4tm1Dgen/J
005771   B6.129P2-Adamts5tm1Dgen/J
005773   B6.129P2-Adcy3tm1Dgen/J
005774   B6.129P2-Adcy7tm1Dgen/J
005775   B6.129P2-Adipor2tm1Dgen/J
005776   B6.129P2-Avpr1atm1Dgen/J
005777   B6.129P2-Axltm1Dgen/J
005783   B6.129P2-Cacna1ctm1Dgen/J
005780   B6.129P2-Cacna2d3tm1Dgen/J
005781   B6.129P2-Cacng3tm1Dgen/J
005782   B6.129P2-Cacng4tm1Dgen/J
005784   B6.129P2-Capn5tm1Dgen/J
005785   B6.129P2-Capn7tm1Dgen/J
005792   B6.129P2-Ccr1l1tm1Dgen/J
005793   B6.129P2-Ccr6tm1Dgen/J
005794   B6.129P2-Ccr7tm1Dgen/J
005779   B6.129P2-Celsr2tm1Dgen/J
005797   B6.129P2-Chrna2tm1Dgen/J
005787   B6.129P2-Ctsctm1Dgen/J
005796   B6.129P2-Cxcr3tm1Dgen/J
005798   B6.129P2-Drd5tm1Dgen/J
005800   B6.129P2-Efemp2tm1Dgen/J
005801   B6.129P2-Esrratm1Dgen/J
005802   B6.129P2-Faim2tm1Dgen/J
005803   B6.129P2-Fzd1tm1Dgen/J
005804   B6.129P2-Fzd8tm1Dgen/J
005811   B6.129P2-Gabra3tm1Dgen/J
005812   B6.129P2-Gabra4tm1Dgen/J
005810   B6.129P2-Gabrptm1Dgen/J
005809   B6.129P2-Galr1tm1Dgen/J
005816   B6.129P2-Glra3tm1Dgen/J
005805   B6.129P2-Gpr151tm1Dgen/J
005806   B6.129P2-Gpr37tm1Dgen/J
005807   B6.129P2-Gpr6tm1Dgen/J
005813   B6.129P2-Grik5tm1Dgen/J
005808   B6.129P2-Grk5tm1Dgen/J
005814   B6.129P2-Grm1tm1Dgen/J
005815   B6.129P2-Grm3tm1Dgen/J
005817   B6.129P2-Gsk3btm1Dgen/J
005818   B6.129P2-Hcrtr1tm1Dgen/J
005767   B6.129P2-Htr4tm1Dgen/J
005769   B6.129P2-Htr7tm1Dgen/J
005830   B6.129P2-Kcnq2tm1Dgen/J
005821   B6.129P2-Lats2tm1Dgen/J
005822   B6.129P2-Lmbr1tm1Dgen/J
005850   B6.129P2-Mapkapk2tm1Dgen/J
005824   B6.129P2-Mmp17tm1Dgen/J
005825   B6.129P2-Mtmr1tm1Dgen/J
005778   B6.129P2-Naip1tm1Dgen/J
005826   B6.129P2-Ntsr1tm1Dgen/J
005829   B6.129P2-Pkd2l2tm1Dgen/J
005828   B6.129P2-Ppardtm1Dgen/J
005831   B6.129P2-Ppm1ftm1Dgen/J
005827   B6.129P2-Ptch2tm1Dgen/J
005832   B6.129P2-Ptprotm1Dgen/J
005799   B6.129P2-S1pr4tm1Dgen/J
005837   B6.129P2-Scn11atm1Dgen/J
005836   B6.129P2-Scn9atm1Dgen/J
005834   B6.129P2-Sema5atm1Dgen/J
005835   B6.129P2-Sema6ctm1Dgen/J
006432   B6.129P2-Slc18a1tm1Dgen/J
005839   B6.129P2-Slc22a12tm1Dgen/J
005838   B6.129P2-Slc22a6tm1Dgen/J
005840   B6.129P2-Slc40a1tm1Dgen/J
005841   B6.129P2-Slc6a9tm1Dgen/J
005842   B6.129P2-Slc7a8tm1Dgen/J
005843   B6.129P2-Slc9a6tm1Dgen/J
005844   B6.129P2-Sstr1tm1Dgen/J
005847   B6.129P2-Tgfbr1tm1Dgen/J
005845   B6.129P2-Thbs4tm1Dgen/J
005790   B6.129P2-Tpp1tm1Dgen/J
005848   B6.129P2-Trpm5tm1Dgen/J
005791   B6.129P2-Xcr1tm1Dgen/J
003474   B6.129S4-Gt(ROSA)26Sortm1Sor/J
005901   B6.129S4-Ppardtm2Rev/J
006142   B6.129S4-Ppargtm1Rev/J
003754   B6.129S4-Shroom3Gt(ROSA)53Sor/J
005119   B6.129S6-Npas2tm1Slm/J
002741   B6.129S7-Alpltm1Sor/J
005970   B6.129S7-Atoh1tm2Hzo/J
006039   B6.129S7-Efnb2tm1And/J
002192   B6.129S7-Gt(ROSA)26Sor/J
005981   B6.129S7-Rai1tm1Jrl/J
005039   B6.129X1-Adra1atm1Pcs/J
006262   B6.129X1-Fut2tm1Sdo/J
005085   B6.Cg-Cd44tm1Hbg/J
007745   B6.Cg-Mirn155tm1.1Rsky/J
005317   B6.Cg-Tg(BAT-lacZ)3Picc/J
006055   B6.Cg-Tg(CAG-Bgeo,-DsRed*MST)1Nagy/J
006477   B6.Cg-Tg(CAG-lacZ-WGA)330Bbm/J
003139   B6.Cg-Tg(DBHn-lacZ)8Rpk/J
006229   B6.Cg-Tg(DRE-lacZ)2Gswz/J
002982   B6.Cg-Tg(xstpx-lacZ)32And/J
003504   B6;129-Gt(ROSA)26Sortm1Sho/J
005064   B6;129-Slc30a3tm1Rpa/J
005788   B6;129P2-Cd97tm1Dgen/J
005833   B6;129P2-Rgs4tm1Dgen/J
002073   B6;129S-Gt(ROSA)26Sor/J
006470   B6;129S-Hopxtm1Eno/J
004153   B6;129S-Mtap7Gt(ROSABetageo)1Sor/J
006958   B6;129S-Nkd1tm1Kwha/J
006960   B6;129S-Nkd2tm1Kwha/J
007204   B6;129S4-2610005L07RikGt(ROSA)73Sor/J
003309   B6;129S4-Gt(ROSA)26Sortm1Sor/J
004365   B6;129S6-Srebf1tm1Mbr/J
002317   B6;129S7-Alpltm1Sor/J
003266   B6;129S7-Epas1tm1Rus/J
006044   B6;129S7-Ephb4tm1And/J
003471   B6;C3H-Tg(CNP-GEO)1Ldh/J
006465   B6;CBA-Tg(CAG-lacZ-WGA)330Bbm/J
006680   B6;CBA-Tg(Olfr16*,taulacZ)19Mom/MomJ
006671   B6;CBA-Tg(Olfr16*,taulacZ)5Mom/MomJ
006672   B6;CBA-Tg(Olfr16*,taulacZ)7Mom/MomJ
006673   B6;CBA-Tg(Olfr16,taulacZ)sn2Mom/MomJ
004141   B6;CBA-Tg(UAS-lacZ)65Rth/J
002369   B6;SJL-Tg(c177-lacZ)226Bri/J
002372   B6;SJL-Tg(c177-lacZ)227Bri/J
002621   B6;SJL-Tg(tetop-lacZ)2Mam/J
003299   B6;SWJ-Tg(TIMP3-lacZ)7Jeb/J
002865   B6CBA-Tg(Wnt1-lacZ)206Amc/J
002955   C.129S7-Gt(ROSA)26Sor/J
002754   C57BL/6-Tg(LacZpl)60Vij/J
002193   C57BL/6J-Tg(MTn-lacZ)204Bri/J
002981   DBA/2-Tg(xstpx-lacZ)36And/J
004127   FVB-Tg(Nes-rtTA)306Rvs/J
007225   FVB.129(B6)-Usp18tm1Dzh/J
008203   FVB.Cg-Smn1tm1Msd Tg(ACTA1-SMN)63Ahmb Tg(SMN2)89Ahmb/J
008209   FVB.Cg-Smn1tm1Msd Tg(ACTA1-SMN)69Ahmb Tg(SMN2)89Ahmb/J
006214   FVB.Cg-Smn1tm1Msd/J
005024   FVB.Cg-Tg(SMN2)89Ahmb Smn1tm1Msd/J
005026   FVB.Cg-Tg(SMN2)89Ahmb Tg(SMN1*A2G)2023Ahmb Smn1tm1Msd/J
005025   FVB.Cg-Tg(SMN2*delta7)4299Ahmb Tg(SMN2)89Ahmb Smn1tm1Msd/J
003140   FVB/N-Tg(PAI1-lacZ)1Jjb/J
002856   FVB/N-Tg(TIE2-lacZ)182Sato/J
005941   FVB/N-Tg(tetO-Aurkb,lacZ)41Kra/J
003315   FVB/N-Tg(tetORo1-lacZ)3Conk/J
003487   FVB/NJ-Tg(XGFAP-lacZ)3Mes/J
005878   NOD.Cg-Cd44tm1Hbg/J
003899   STOCK Cd44tm1Hbg/J
006241   STOCK Hhiptm1Amc/J
006578   STOCK Myoz2tm1Eno/J
005707   STOCK Rag1tm1Mom Tg(TIE2-lacZ)182Sato/J
008212   STOCK Smn1tm1Msd Tg(Prnp-SMN)92Ahmb Tg(SMN2)89Ahmb/J
006882   STOCK Tg(CAG-Bgeo,-AML1/ETO,-ALPP)1Lbe/J
005438   STOCK Tg(CAG-Bgeo,-DsRed*MST)1Nagy/J
006850   STOCK Tg(CAG-Bgeo,-NOTCH1,-EGFP)1Lbe/J
006876   STOCK Tg(CAG-Bgeo,-TEL/AML1,-EGFP)A6Lbe/J
006613   STOCK Tg(CAG-Bgeo,-Tle1,-ALPP)1Lbe/J
003919   STOCK Tg(CAG-Bgeo/ALPP)1Lbe/J
003920   STOCK Tg(CAG-Bgeo/GFP)21Lbe/J
004623   STOCK Tg(Fos-lacZ)34Efu/J
006674   STOCK Tg(Olfr16,taulacZ)2030Mom/MomJ
005493   STOCK Tg(Tek-rtTA,TRE-lacZ)1425Tpr/J
002395   STOCK Tg(Zfy1-lacZ)218Bri/J
003274   STOCK Tg(tetNZL)2Bjd/J
005728   STOCK Tg(tetO-Ipf1,lacZ)958.1Macd/J
View lacZ Expression Strains     (174 strains)

Additional Web Information

Fluorescent Proteins/lacZ Systems

Animal Health Reports

Room Number           AX11

Research Applications

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

Apoptosis Research
Endogenous Regulators

Cancer Research
Other (DNA Repair)

Cardiovascular Research
Other (altered fat metabolism)

Cell Biology Research
DNA Damage Response

Immunology and Inflammation Research
Immunodeficiency (Inflammatory bowel disease)
Inflammation (Inflammatory bowel disease)
Lymphoid Tissue Defects

Internal/Organ Research
Gastrointestinal Defects (colitis)
Lymphoid Tissue Defects

Research Tools
lacZ Expression
Apoptosis Research
Internal/Organ Research
Metabolism Research

References

Selected Reference(s)

Mostoslavsky R; Chua KF; Lombard DB; Pang WW; Fischer MR; Gellon L; Liu P; Mostoslavsky G; Franco S; Murphy MM; Mills KD; Patel P; Hsu JT; Hong AL; Ford E; Cheng HL; Kennedy C; Nunez N; Bronson R; Frendewey D; Auerbach W; Valenzuela D; Karow M; Hottiger MO; Hursting S; Barrett JC; Guarente L; Mulligan R; Demple B; Yancopoulos GD; Alt FW. 2006. Genomic instability and aging-like phenotype in the absence of mammalian SIRT6. Cell 124(2):315-29. [PubMed: 16439206]  [MGI Ref ID J:112817]

Price and Supply Information

Strain Name: 129-Sirt6tm1Fwa/J
Stock Number: 006050

Price Details

IMPORTANT NOTE: Prices are based on shipping destination. The shipping destinations are:

*Pricing for Shipping Destination selected:

        International

Price(s) in US dollars ($)Genotype(s) Provided
Individual Mouse Price $307.40Heterozygous for Sirt6tm1Fwa
Pair $375.30Heterozygous for Sirt6tm1Fwa x Wild-type for Sirt6tm1Fwa
Pair $375.30Wild-type for Sirt6tm1Fwa x Heterozygous for Sirt6tm1Fwa

Supply Details

Standard SupplyRepository-Live. A collection of over 1000 strains maintained as live colonies. Individual colonies are sized to meet current customer demand. Delivery for orders of 10 mice or less ranges on average from one to eight weeks; mice are generally shipped between four to six weeks of age with a maximum shipping age of ~nine weeks. Colony sizes do not generally support stringent age specifications for large volumes of mice; however custom orders and larger quantities of mice are easily arranged. Estimated ship dates for all orders provided within 48 hours of order placement.
Supply Notes Histology and Tissue Collection Services are available for all JAX® Mice strains. For more information, please contact Customer Service at orderquest@jax.org or 1-207-288-5845.
Usually shipped between four and eight weeks of age.
This strain is included in the Induced Mutant Resource Colony collection.
LicensingSee General Terms and Conditions below for Licensing and Use Restrictions  
Control InformationView Control Information in Strain Details.
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- Strain(s) not available to companies or for-profit entities.

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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.
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