Strain Name:

STOCK Foxo3tm1Rdp/J

Stock Number:

024668

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Availability:

Repository- Live

Use Restrictions Apply, see Terms of Use
Foxo3L/L floxed mice may be useful for studying the regulatory role of the FOXO3 transcription factor on cell survival and tumor suppression.

Description

Strain Information

Former Names FVB.129S6(Cg)-Foxo3tm1Rdp/J    (Changed: 01-DEC-14 )
Type Mutant Stock; Targeted Mutation;
Additional information on Genetically Engineered and Mutant Mice.
Visit our online Nomenclature tutorial.
Mating SystemHeterozygote x Heterozygote         (Female x Male)   21-APR-14
Specieslaboratory mouse
GenerationN3+pN1 (30-JUN-14)
Generation Definitions
 
Donating InvestigatorDr. Ronald DePinho,   MD Anderson Cancer Center

Description
These Foxo3L/L mutant mice possess loxP sites flanking exon 2 of the forkhead box O3 (Foxo3) gene. FOXO3 is a transcription factor which regulates the expression of genes involved in stress resistance, cell cycle progression, tumor progression, longevity, autophagy, and apoptosis. FOXO3 has also been shown to be a tumor suppressor. Mice that are homozygous for this allele are viable and fertile. When these mutant mice are bred to mice that express Cre recombinase, the resulting offspring will have exon 2 deleted in the cre-expressing tissue, resulting in inactivation of Foxo3 gene expression.

Development
A targeting vector was designed to insert a loxP site, followed by a frt-flanked neomycin resistance (neo) cassette upstream of exon 2, and a single loxP site downstream of exon 2 of the forkhead box O3 (Foxo3) gene. The construct was electroporated into 129S6/SvEvTac-derived TC1 embryonic stem (ES) cells. Correctly targeted ES cells were injected into blastocysts and resulting chimeric mice were bred to FVB/N mice to establish a colony. The donating investigator reported that mice were bred to FVB mice for at least 3 generations before being bred with mice carrying Foxo4tm1Rdp and Foxo1tm1Rdp (see SNP note below). Upon arrival, mice were bred to FVB/NJ inbred mice (Stock No. 001800) for at least one generation to establish the colony. The three alleles in this strain were separated and maintained as separate strains (for Foxo4tm1Rdp see Stock No. 024757 and for Foxo1tm1Rdp see Stock No. 024756). Single mutants were bred to FVB/NJ for at least one more generation.

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. Three of the 27 markers throughout the genome were segregating, suggesting an incomplete backcross.

Control Information

  Control
   001800 FVB/NJ (approximate)
 
  Considerations for Choosing Controls

Related Strains

Strains carrying other alleles of Foxo3
022097   B6N(Cg)-Foxo3tm1.1(KOMP)Vlcg/J
View Strains carrying other alleles of Foxo3     (1 strain)

Phenotype

Phenotype Information

View Mammalian Phenotype Terms

Mammalian Phenotype Terms provided by MGI
      assigned by genotype

The following phenotype relates to a compound genotype created using this strain.
Contact JAX® Services jaxservices@jax.org for customized breeding options.

Foxo3tm1Rdp/Foxo3tm1Rdp Tg(Ddx4-cre)1Dcas/0

        involves: 129S6/SvEvTac * FVB/N   (conditional)
  • endocrine/exocrine gland phenotype
  • abnormal ovary physiology
    • ovaries explanted at birth and cultured for 8 days grow more rapidly than controls   (MGI Ref ID J:138697)
  • abnormal primordial ovarian follicle morphology
    • global primordial follicle activation   (MGI Ref ID J:138697)
  • enlarged ovary   (MGI Ref ID J:138697)
  • reproductive system phenotype
  • abnormal ovary physiology
    • ovaries explanted at birth and cultured for 8 days grow more rapidly than controls   (MGI Ref ID J:138697)
  • abnormal primordial ovarian follicle morphology
    • global primordial follicle activation   (MGI Ref ID J:138697)
  • enlarged ovary   (MGI Ref ID J:138697)
View Research Applications

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

Apoptosis Research

Cell Biology Research
Cell Cycle Regulation

Research Tools
Cre-lox System
      loxP-flanked Sequences

Genes & Alleles

Gene & Allele Information provided by MGI

 
Allele Symbol Foxo3tm1Rdp
Allele Name targeted mutation 1, Ronald DePinho
Allele Type Targeted (Conditional ready (e.g. floxed), No functional change)
Common Name(s) FoxO3L; Foxo3f;
Strain of Origin129S6/SvEvTac
Gene Symbol and Name Foxo3, forkhead box O3
Chromosome 10
Gene Common Name(s) 1110048B16Rik; 2010203A17Rik; C76856; FKHRL1; Fkhr2; Foxo3a; RIKEN cDNA 1110048B16 gene; RIKEN cDNA 2010203A17 gene; expressed sequence C76856;
Molecular Note Exon 2, which is the first coding exon, was flanked by a loxP-frt-neo-frt cassette in intron 1 and single loxP site in intron 2. Mice carrying this allele were bred with cre transgenic mice to generate Foxo3tm1.1Rdp. [MGI Ref ID J:84269]

Genotyping

Genotyping Information

Genotyping Protocols

Foxo1tm1Rdp, Standard PCR
Foxo3tm1Rdp, Standard PCR
Foxo4tm1Rdp, Standard PCR
Generic Cre Melt Curve Analysis,

MELT


Generic Cre Melt Curve Analysis,

Probe


Generic Neo Melt Curve Analysis,

MELT


Tg(ACTFLPe),

Probe


Tg(ACTFLPe), High Resolution Melting


Helpful Links

Genotyping resources and troubleshooting

References

References provided by MGI

Selected Reference(s)

Castrillon DH; Miao L; Kollipara R; Horner JW; DePinho RA. 2003. Suppression of ovarian follicle activation in mice by the transcription factor Foxo3a. Science 301(5630):215-8. [PubMed: 12855809]  [MGI Ref ID J:84269]

Additional References

Foxo3tm1Rdp related

Ambrogini E; Almeida M; Martin-Millan M; Paik JH; Depinho RA; Han L; Goellner J; Weinstein RS; Jilka RL; O'Brien CA; Manolagas SC. 2010. FoxO-mediated defense against oxidative stress in osteoblasts is indispensable for skeletal homeostasis in mice. Cell Metab 11(2):136-46. [PubMed: 20142101]  [MGI Ref ID J:158622]

Bartell SM; Kim HN; Ambrogini E; Han L; Iyer S; Serra Ucer S; Rabinovitch P; Jilka RL; Weinstein RS; Zhao H; O'Brien CA; Manolagas SC; Almeida M. 2014. FoxO proteins restrain osteoclastogenesis and bone resorption by attenuating H2O2 accumulation. Nat Commun 5:3773. [PubMed: 24781012]  [MGI Ref ID J:208828]

Battiprolu PK; Hojayev B; Jiang N; Wang ZV; Luo X; Iglewski M; Shelton JM; Gerard RD; Rothermel BA; Gillette TG; Lavandero S; Hill JA. 2012. Metabolic stress-induced activation of FoxO1 triggers diabetic cardiomyopathy in mice. J Clin Invest 122(3):1109-18. [PubMed: 22326951]  [MGI Ref ID J:184484]

Dejean AS; Beisner DR; Ch'en IL; Kerdiles YM; Babour A; Arden KC; Castrillon DH; DePinho RA; Hedrick SM. 2009. Transcription factor Foxo3 controls the magnitude of T cell immune responses by modulating the function of dendritic cells. Nat Immunol 10(5):504-13. [PubMed: 19363483]  [MGI Ref ID J:148279]

Deng X; Zhang W; O-Sullivan I; Williams JB; Dong Q; Park EA; Raghow R; Unterman TG; Elam MB. 2012. FoxO1 inhibits sterol regulatory element-binding protein-1c (SREBP-1c) gene expression via transcription factors Sp1 and SREBP-1c. J Biol Chem 287(24):20132-43. [PubMed: 22511764]  [MGI Ref ID J:186518]

Gan B; Lim C; Chu G; Hua S; Ding Z; Collins M; Hu J; Jiang S; Fletcher-Sananikone E; Zhuang L; Chang M; Zheng H; Wang YA; Kwiatkowski DJ; Kaelin WG Jr; Signoretti S; DePinho RA. 2010. FoxOs enforce a progression checkpoint to constrain mTORC1-activated renal tumorigenesis. Cancer Cell 18(5):472-84. [PubMed: 21075312]  [MGI Ref ID J:166830]

Goertz MJ; Wu Z; Gallardo TD; Hamra FK; Castrillon DH. 2011. Foxo1 is required in mouse spermatogonial stem cells for their maintenance and the initiation of spermatogenesis. J Clin Invest 121(9):3456-66. [PubMed: 21865646]  [MGI Ref ID J:178240]

Haeusler RA; Kaestner KH; Accili D. 2010. FoxOs function synergistically to promote glucose production. J Biol Chem 285(46):35245-8. [PubMed: 20880840]  [MGI Ref ID J:167017]

Haeusler RA; Pratt-Hyatt M; Welch CL; Klaassen CD; Accili D. 2012. Impaired generation of 12-hydroxylated bile acids links hepatic insulin signaling with dyslipidemia. Cell Metab 15(1):65-74. [PubMed: 22197325]  [MGI Ref ID J:182348]

Herzog S; Hug E; Meixlsperger S; Paik JH; DePinho RA; Reth M; Jumaa H. 2008. SLP-65 regulates immunoglobulin light chain gene recombination through the PI(3)K-PKB-Foxo pathway. Nat Immunol 9(6):623-31. [PubMed: 18488031]  [MGI Ref ID J:136355]

Iyer S; Ambrogini E; Bartell SM; Han L; Roberson PK; de Cabo R; Jilka RL; Weinstein RS; O'Brien CA; Manolagas SC; Almeida M. 2013. FOXOs attenuate bone formation by suppressing Wnt signaling. J Clin Invest 123(8):3409-19. [PubMed: 23867625]  [MGI Ref ID J:201398]

John GB; Gallardo TD; Shirley LJ; Castrillon DH. 2008. Foxo3 is a PI3K-dependent molecular switch controlling the initiation of oocyte growth. Dev Biol 321(1):197-204. [PubMed: 18601916]  [MGI Ref ID J:138697]

Lin A; Yao J; Zhuang L; Wang D; Han J; Lam EW; Gan B. 2014. The FoxO-BNIP3 axis exerts a unique regulation of mTORC1 and cell survival under energy stress. Oncogene 33(24):3183-94. [PubMed: 23851496]  [MGI Ref ID J:212581]

Ouyang W; Beckett O; Ma Q; Paik JH; DePinho RA; Li MO. 2010. Foxo proteins cooperatively control the differentiation of Foxp3+ regulatory T cells. Nat Immunol 11(7):618-27. [PubMed: 20467422]  [MGI Ref ID J:161859]

Paik JH; Ding Z; Narurkar R; Ramkissoon S; Muller F; Kamoun WS; Chae SS; Zheng H; Ying H; Mahoney J; Hiller D; Jiang S; Protopopov A; Wong WH; Chin L; Ligon KL; DePinho RA. 2009. FoxOs cooperatively regulate diverse pathways governing neural stem cell homeostasis. Cell Stem Cell 5(5):540-53. [PubMed: 19896444]  [MGI Ref ID J:154024]

Paik JH; Kollipara R; Chu G; Ji H; Xiao Y; Ding Z; Miao L; Tothova Z; Horner JW; Carrasco DR; Jiang S; Gilliland DG; Chin L; Wong WH; Castrillon DH; DePinho RA. 2007. FoxOs are lineage-restricted redundant tumor suppressors and regulate endothelial cell homeostasis. Cell 128(2):309-23. [PubMed: 17254969]  [MGI Ref ID J:118179]

Park Y; Jin HS; Lopez J; Elly C; Kim G; Murai M; Kronenberg M; Liu YC. 2013. TSC1 regulates the balance between effector and regulatory T cells. J Clin Invest 123(12):5165-78. [PubMed: 24270422]  [MGI Ref ID J:207832]

Rached MT; Kode A; Xu L; Yoshikawa Y; Paik JH; Depinho RA; Kousteni S. 2010. FoxO1 is a positive regulator of bone formation by favoring protein synthesis and resistance to oxidative stress in osteoblasts. Cell Metab 11(2):147-60. [PubMed: 20142102]  [MGI Ref ID J:158621]

Ren H; Plum-Morschel L; Gutierrez-Juarez R; Lu TY; Kim-Muller JY; Heinrich G; Wardlaw SL; Silver R; Accili D. 2013. Blunted refeeding response and increased locomotor activity in mice lacking FoxO1 in synapsin-Cre-expressing neurons. Diabetes 62(10):3373-83. [PubMed: 23835335]  [MGI Ref ID J:208948]

Renault VM; Rafalski VA; Morgan AA; Salih DA; Brett JO; Webb AE; Villeda SA; Thekkat PU; Guillerey C; Denko NC; Palmer TD; Butte AJ; Brunet A. 2009. FoxO3 regulates neural stem cell homeostasis. Cell Stem Cell 5(5):527-39. [PubMed: 19896443]  [MGI Ref ID J:154025]

Rosborough BR; Raich-Regue D; Matta BM; Lee K; Gan B; DePinho RA; Hackstein H; Boothby M; Turnquist HR; Thomson AW. 2013. Murine dendritic cell rapamycin-resistant and rictor-independent mTOR controls IL-10, B7-H1, and regulatory T-cell induction. Blood 121(18):3619-30. [PubMed: 23444404]  [MGI Ref ID J:197572]

Roupe KM; Veerla S; Olson J; Stone EL; Sorensen OE; Hedrick SM; Nizet V. 2014. Transcription factor binding site analysis identifies FOXO transcription factors as regulators of the cutaneous wound healing process. PLoS One 9(2):e89274. [PubMed: 24586650]  [MGI Ref ID J:213755]

Sengupta A; Molkentin JD; Paik JH; DePinho RA; Yutzey KE. 2011. FoxO transcription factors promote cardiomyocyte survival upon induction of oxidative stress. J Biol Chem 286(9):7468-78. [PubMed: 21159781]  [MGI Ref ID J:170395]

Sullivan JA; Kim EH; Plisch EH; Peng SL; Suresh M. 2012. FOXO3 regulates CD8 T cell memory by T cell-intrinsic mechanisms. PLoS Pathog 8(2):e1002533. [PubMed: 22359505]  [MGI Ref ID J:195402]

Sykes SM; Lane SW; Bullinger L; Kalaitzidis D; Yusuf R; Saez B; Ferraro F; Mercier F; Singh H; Brumme KM; Acharya SS; Scholl C; Tothova Z; Attar EC; Frohling S; Depinho RA; Armstrong SA; Gilliland DG; Scadden DT. 2011. AKT/FOXO Signaling Enforces Reversible Differentiation Blockade in Myeloid Leukemias. Cell 146(5):697-708. [PubMed: 21884932]  [MGI Ref ID J:176214]

Tao R; Wei D; Gao H; Liu Y; Depinho RA; Dong XC. 2011. Hepatic FoxOs Regulate Lipid Metabolism via Modulation of Expression of the Nicotinamide Phosphoribosyltransferase Gene. J Biol Chem 286(16):14681-90. [PubMed: 21388966]  [MGI Ref ID J:171118]

Tao R; Xiong X; DePinho RA; Deng CX; Dong XC. 2013. FoxO3 transcription factor and Sirt6 deacetylase regulate low density lipoprotein (LDL)-cholesterol homeostasis via control of the proprotein convertase subtilisin/kexin type 9 (Pcsk9) gene expression. J Biol Chem 288(41):29252-9. [PubMed: 23974119]  [MGI Ref ID J:203942]

Tao R; Xiong X; DePinho RA; Deng CX; Dong XC. 2013. Hepatic SREBP-2 and cholesterol biosynthesis are regulated by FoxO3 and Sirt6. J Lipid Res 54(10):2745-53. [PubMed: 23881913]  [MGI Ref ID J:202625]

Tothova Z; Kollipara R; Huntly BJ; Lee BH; Castrillon DH; Cullen DE; McDowell EP; Lazo-Kallanian S; Williams IR; Sears C; Armstrong SA; Passegue E; DePinho RA; Gilliland DG. 2007. FoxOs are critical mediators of hematopoietic stem cell resistance to physiologic oxidative stress. Cell 128(2):325-39. [PubMed: 17254970]  [MGI Ref ID J:117892]

Tsuchiya K; Accili D. 2013. Liver sinusoidal endothelial cells link hyperinsulinemia to hepatic insulin resistance. Diabetes 62(5):1478-89. [PubMed: 23349480]  [MGI Ref ID J:208573]

Tsuchiya K; Tanaka J; Shuiqing Y; Welch CL; DePinho RA; Tabas I; Tall AR; Goldberg IJ; Accili D. 2012. FoxOs integrate pleiotropic actions of insulin in vascular endothelium to protect mice from atherosclerosis. Cell Metab 15(3):372-81. [PubMed: 22405072]  [MGI Ref ID J:182672]

Tsuchiya K; Westerterp M; Murphy AJ; Subramanian V; Ferrante AW Jr; Tall AR; Accili D. 2013. Expanded granulocyte/monocyte compartment in myeloid-specific triple FoxO knockout increases oxidative stress and accelerates atherosclerosis in mice. Circ Res 112(7):992-1003. [PubMed: 23420833]  [MGI Ref ID J:213325]

Webb AE; Pollina EA; Vierbuchen T; Urban N; Ucar D; Leeman DS; Martynoga B; Sewak M; Rando TA; Guillemot F; Wernig M; Brunet A. 2013. FOXO3 shares common targets with ASCL1 genome-wide and inhibits ASCL1-dependent neurogenesis. Cell Rep 4(3):477-91. [PubMed: 23891001]  [MGI Ref ID J:201905]

Xiong X; Tao R; DePinho RA; Dong XC. 2012. The autophagy-related gene 14 (Atg14) is regulated by forkhead box O transcription factors and circadian rhythms and plays a critical role in hepatic autophagy and lipid metabolism. J Biol Chem 287(46):39107-14. [PubMed: 22992773]  [MGI Ref ID J:192959]

Yeo H; Lyssiotis CA; Zhang Y; Ying H; Asara JM; Cantley LC; Paik JH. 2013. FoxO3 coordinates metabolic pathways to maintain redox balance in neural stem cells. EMBO J 32(19):2589-602. [PubMed: 24013118]  [MGI Ref ID J:202479]

Zhang K; Li L; Qi Y; Zhu X; Gan B; DePinho RA; Averitt T; Guo S. 2012. Hepatic suppression of Foxo1 and Foxo3 causes hypoglycemia and hyperlipidemia in mice. Endocrinology 153(2):631-46. [PubMed: 22147007]  [MGI Ref ID J:181743]

Health & husbandry

Health & Colony Maintenance Information

Animal Health Reports

Room Number           AX18

Colony Maintenance

Breeding & HusbandryWhen maintaining a live colony homozygous mice may be bred together.
Mating SystemHeterozygote x Heterozygote         (Female x Male)   21-APR-14

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 $232.00Female or MaleHeterozygous for Foxo3tm1Rdp  
$232.00Female or MaleHomozygous for Foxo3tm1Rdp  
Price per Pair (US dollars $)Pair Genotype
$464.00Heterozygous for Foxo3tm1Rdp x Heterozygous for Foxo3tm1Rdp  

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 $301.60Female or MaleHeterozygous for Foxo3tm1Rdp  
$301.60Female or MaleHomozygous for Foxo3tm1Rdp  
Price per Pair (US dollars $)Pair Genotype
$603.20Heterozygous for Foxo3tm1Rdp x Heterozygous for Foxo3tm1Rdp  

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
   001800 FVB/NJ (approximate)
 
  Considerations for Choosing Controls
  Control Pricing Information for Genetically Engineered Mutant Strains.
 

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