Description

Strain Information

Type Mutant Stock; Targeted Mutation; Additional information on Genetically Engineered and Mutant Mice. Visit our online Nomenclature tutorial. Mating System Homozygote x Homozygote         (Female x Male)   20-OCT-08 Species laboratory mouse Generation ?+F8 (11-MAY-11) Generation Definitions   Donating Investigator Dr. Yansong Gu,   University of Washington School of Med.

Description
Mice homozygous for this targeted allele (SirT1^co/co) are viable and fertile. A loxP-flanked neomycin cassette just upstream of exon 4 and a third loxP site downstream of exon 4 were inserted to create this targeted mutant Sirt1 allele. The floxed mutation does not affect SIRT1 protein expression in MEFs or mammary gland tissue in homozygotes. When bred to mice that express Cre recombinase, the resulting offspring have exon 4 (encoding an evolutionarily conserved Sir2 motif) deleted in cre-expressing tissue(s); (the donating investigator reports only one recombination event: complete removal of the neomycin cassette and exon 4, leaving a single loxp). These SirT1^co/co mice may be useful in generating conditional mutants for studying transcriptional regulation and the role of estrogen, insulin growth factor-1 (IGF-1), and transcription factors (including NF-kappaB) in mammary gland development, mammary cancer, apoptosis, and metabolic diseases.

Development
A targeting vector was designed to insert a loxP-flanked, reverse-oriented neomycin cassette just upstream of exon 4 and a third loxP site downstream of exon 4 of the targeted gene. The construct was electroporated into (129X1/SvJ x 129S1/Sv)F1-derived R1 embryonic stem (ES) cells. Correctly targeted ES cells were injected into C57BL/6 blastocysts and the chimeras were bred with C57BL/6 mice. The resulting heterozygotes were interbred to generate homozygous SirT1^co/co mice on this mixed B6;129 genetic background. Homozygotes were interbred for many generations prior to arrival at The Jackson Laboratory.

Control Information

	Control
	101043 B6129SF1/J	(approximate)
	101045 B6129SF2/J	(approximate)
Considerations for Choosing Controls

Related Strains

Strains carrying   Sirt1^tm1Ygu allele

008081

CBy.129(B6)-Sirt1tm1Ygu/J

View Strains carrying   Sirt1^tm1Ygu     (1 strain)

Strains carrying other alleles of Sirt1

013080

C57BL/6-Actbtm3.1(Sirt1)Npa/J

View Strains carrying other alleles of Sirt1     (1 strain)

Additional Web Information

Introduction to Cre-lox technology

Phenotype

Phenotype Information

View Mammalian Phenotype Terms

Mammalian Phenotype Terms provided by MGI

      assigned by genotype

Sirt1^tm1Ygu/Sirt1^tm1Ygu

        involves: 129/Sv * C57BL/6

• normal phenotype
• no abnormal phenotype detected   (MGI Ref ID J:121948)

View Research Applications

Research Applications

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

Cancer Research
Growth Factors/Receptors/Cytokines
Other

Cell Biology Research
Transcriptional Regulation

Diabetes and Obesity Research
Insulin Receptors and Growth Factors

Endocrine Deficiency Research
Mammary Gland Defects

Research Tools
Apoptosis Research
Cancer Research
Cell Biology Research
Cre-lox System
      loxP-flanked Sequences
Diabetes and Obesity Research
      loxP
Genetics Research
      Mutagenesis and Transgenesis
      Mutagenesis and Transgenesis: transcriptional activation
Metabolism Research

Genes & Alleles

Gene & Allele Information provided by MGI

Allele Symbol		Sirt1tm1Ygu
Allele Name		targeted mutation 1, Yansong Gu
Allele Type		Targeted (Floxed/Frt)
Common Name(s)		SirT1co; Sirt1flox;
Mutation Made By		Dr. Yansong Gu,   University of Washington School of Med.
Strain of Origin		(129X1/SvJ x 129S1/Sv)F1-Kitl<+>
ES Cell Line Name		R1
ES Cell Line Strain		(129X1/SvJ x 129S1/Sv)F1-Kitl<+>
Gene Symbol and Name		Sirt1, sirtuin 1 (silent mating type information regulation 2, homolog) 1 (S. cerevisiae)
Chromosome		10
Gene Common Name(s)		AA673258; SIR2L1; Sir2; Sir2alpha; expressed sequence AA673258;
Molecular Note		A floxed neomycin cassette was inserted just upstream of exon 4 and a third loxP site was inserted just downstream. The floxed mutation does not affect the protein expression of the targeted gene in MEF's or mammary tissue from homozygotes. When bred tomice that express Cre recombinase, the resulting offspring will have exon 4 (encoding a conserved Sir2 motif) deleted in the cre-expressing tissue(s). [MGI Ref ID J:121948] [MGI Ref ID J:85542]

Genotyping

Genotyping Information

Genotyping Protocols

Sirt1^tm1Ygu, Standard PCR

Helpful Links

Genotyping resources and troubleshooting

References

References provided by MGI

Selected Reference(s)

Li H; Rajendran GK; Liu N; Ware C; Rubin BP; Gu Y. 2007. SirT1 modulates the estrogen-insulin-like growth factor-1 signaling for postnatal development of mammary gland in mice. Breast Cancer Res 9(1):R1. [PubMed: 17201918]  [MGI Ref ID J:121948]

Additional References

Sirt1^tm1Ygu related

Chen D; Bruno J; Easlon E; Lin SJ; Cheng HL; Alt FW; Guarente L. 2008. Tissue-specific regulation of SIRT1 by calorie restriction. Genes Dev 22(13):1753-7. [PubMed: 18550784]  [MGI Ref ID J:137371]

Cheng HL; Mostoslavsky R; Saito S; Manis JP; Gu Y; Patel P; Bronson R; Appella E; Alt FW; Chua KF. 2003. Developmental defects and p53 hyperacetylation in Sir2 homolog (SIRT1)-deficient mice. Proc Natl Acad Sci U S A 100(19):10794-9. [PubMed: 12960381]  [MGI Ref ID J:85542]

Dietrich MO; Antunes C; Geliang G; Liu ZW; Borok E; Nie Y; Xu AW; Souza DO; Gao Q; Diano S; Gao XB; Horvath TL. 2010. Agrp neurons mediate Sirt1's action on the melanocortin system and energy balance: roles for Sirt1 in neuronal firing and synaptic plasticity. J Neurosci 30(35):11815-25. [PubMed: 20810901]  [MGI Ref ID J:164001]

Dietrich MO; Bober J; Ferreira JG; Tellez LA; Mineur YS; Souza DO; Gao XB; Picciotto MR; Araujo I; Liu ZW; Horvath TL. 2012. AgRP neurons regulate development of dopamine neuronal plasticity and nonfood-associated behaviors. Nat Neurosci 15(8):1108-10. [PubMed: 22729177]  [MGI Ref ID J:191603]

Herranz D; Serrano M. 2010. SIRT1: recent lessons from mouse models. Nat Rev Cancer 10(12):819-23. [PubMed: 21102633]  [MGI Ref ID J:166994]

Hsu CP; Zhai P; Yamamoto T; Maejima Y; Matsushima S; Hariharan N; Shao D; Takagi H; Oka S; Sadoshima J. 2010. Silent information regulator 1 protects the heart from ischemia/reperfusion. Circulation 122(21):2170-82. [PubMed: 21060073]  [MGI Ref ID J:179477]

Legutko A; Marichal T; Fievez L; Bedoret D; Mayer A; de Vries H; Klotz L; Drion PV; Heirman C; Cataldo D; Louis R; Thielemans K; Andris F; Leo O; Lekeux P; Desmet CJ; Bureau F. 2011. Sirtuin 1 promotes Th2 responses and airway allergy by repressing peroxisome proliferator-activated receptor-gamma activity in dendritic cells. J Immunol 187(9):4517-29. [PubMed: 21948987]  [MGI Ref ID J:179447]

Liu Y; Dentin R; Chen D; Hedrick S; Ravnskjaer K; Schenk S; Milne J; Meyers DJ; Cole P; Yates J rd; Olefsky J; Guarente L; Montminy M. 2008. A fasting inducible switch modulates gluconeogenesis via activator/coactivator exchange. Nature 456(7219):269-73. [PubMed: 18849969]  [MGI Ref ID J:141418]

Oka S; Alcendor R; Zhai P; Park JY; Shao D; Cho J; Yamamoto T; Tian B; Sadoshima J. 2011. PPARalpha-Sirt1 complex mediates cardiac hypertrophy and failure through suppression of the ERR transcriptional pathway. Cell Metab 14(5):598-611. [PubMed: 22055503]  [MGI Ref ID J:179686]

Panossian L; Fenik P; Zhu Y; Zhan G; McBurney MW; Veasey S. 2011. SIRT1 Regulation of Wakefulness and Senescence-Like Phenotype in Wake Neurons. J Neurosci 31(11):4025-36. [PubMed: 21411645]  [MGI Ref ID J:170455]

Purushotham A; Schug TT; Xu Q; Surapureddi S; Guo X; Li X. 2009. Hepatocyte-specific deletion of SIRT1 alters fatty acid metabolism and results in hepatic steatosis and inflammation. Cell Metab 9(4):327-38. [PubMed: 19356714]  [MGI Ref ID J:148170]

Purushotham A; Xu Q; Lu J; Foley JF; Yan X; Kim DH; Kemper JK; Li X. 2012. Hepatic deletion of SIRT1 decreases hepatocyte nuclear factor 1alpha/farnesoid X receptor signaling and induces formation of cholesterol gallstones in mice. Mol Cell Biol 32(7):1226-36. [PubMed: 22290433]  [MGI Ref ID J:183692]

Schug TT; Xu Q; Gao H; Peres-da-Silva A; Draper DW; Fessler MB; Purushotham A; Li X. 2010. Myeloid deletion of SIRT1 induces inflammatory signaling in response to environmental stress. Mol Cell Biol 30(19):4712-21. [PubMed: 20647536]  [MGI Ref ID J:164917]

Vila-Brau A; De Sousa-Coelho AL; Mayordomo C; Haro D; Marrero PF. 2011. Human HMGCS2 Regulates Mitochondrial Fatty Acid Oxidation and FGF21 Expression in HepG2 Cell Line. J Biol Chem 286(23):20423-30. [PubMed: 21502324]  [MGI Ref ID J:173493]

Wu Z; Liu MC; Liang M; Fu J. 2012. Sirt1 protects against thrombomodulin down-regulation and lung coagulation after particulate matter exposure. Blood 119(10):2422-9. [PubMed: 22262770]  [MGI Ref ID J:182540]

Yao H; Chung S; Hwang JW; Rajendrasozhan S; Sundar IK; Dean DA; McBurney MW; Guarente L; Gu W; Ronty M; Kinnula VL; Rahman I. 2012. SIRT1 protects against emphysema via FOXO3-mediated reduction of premature senescence in mice. J Clin Invest 122(6):2032-45. [PubMed: 22546858]  [MGI Ref ID J:188297]

Health & husbandry

Health & Colony Maintenance Information

Animal Health Reports

Room Number           AX12

Colony Maintenance

Breeding & Husbandry	When maintaining a live colony, homozygous mice may be bred together.
Mating System	Homozygote x Homozygote         (Female x Male)   20-OCT-08
Diet Information	LabDiet® 5K52/5K67

Pricing and Purchasing

Pricing, Supply Level & Notes, Controls

General Supply Notes

• Genomic DNA is available for this strain from the Mouse DNA Resource.

Control Information

	Control
	101043 B6129SF1/J	(approximate)
	101045 B6129SF2/J	(approximate)
Considerations for Choosing Controls
Control Pricing Information for Genetically Engineered Mutant Strains.

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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.

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