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Under Development - Now Accepting Orders

Estimated Available for Distribution Date: 22-DEC-14
Use Restrictions Apply, see Terms of Use
Foxo4L/L floxed mice may be useful for studying the regulatory role of the FOXO4 transcription factor on insulin signaling and tumor suppression.


Strain Information

Type Congenic; Mutant Strain; Targeted Mutation;
Additional information on Genetically Engineered and Mutant Mice.
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Additional information on Congenic nomenclature.
Mating SystemHeterozygote (F) x Hemizygote         (Female x Male)   21-APR-14
Specieslaboratory mouse
GenerationN3+pN1 (30-JUN-14)
Generation Definitions
Donating InvestigatorDr. Ronald DePinho,   MD Anderson Cancer Center

These Foxo4L/L mutant mice possess loxP sites flanking exon 1 of the forkhead box O4 (Foxo4) gene. FOXO4 is a transcription factor involved in the regulation of insulin signaling, and is involved in tumor suppression by promoting cell cycle arrest and apoptosis. 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 1 deleted in the cre-expressing tissue, resulting in inactivation of Foxo4 gene expression.

A targeting vector was designed to insert a loxP site upstream of exon 1, and a frt-flanked neomycin resistance (neo) cassette followed by a second loxP site downstream of exon 1 of the forkhead box O4 (Foxo4) 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 Tg(ACTFLPe)9205Dym transgenic mice to delete the neo cassette. Progeny were crossed to remove the Flp-expressing transgene. Mice were bred to FVB mice for at least 3 generations before being bred with mice carrying Foxo1tm1Rdp and Foxo3tm1Rdp. 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 Foxo1tm1Rdp see Stock No. 024756 and for Foxo3tm1Rdp see Stock No. 024668). Single mutants were bred to FVB/NJ for at least one more generation.

Control Information

   001800 FVB/NJ
  Considerations for Choosing Controls


Phenotype Information

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
Transcriptional Regulation

Diabetes and Obesity Research

Research Tools
Cre-lox System
      loxP-flanked Sequences
Diabetes and Obesity Research

Genes & Alleles

Gene & Allele Information provided by MGI

Allele Symbol Foxo4tm1Rdp
Allele Name targeted mutation 1, Ronald DePinho
Allele Type Targeted (Conditional ready (e.g. floxed), No functional change)
Common Name(s) FoxO4L; Foxo4F;
Strain of Origin129S6/SvEvTac
Gene Symbol and Name Foxo4, forkhead box O4
Chromosome X
Gene Common Name(s) AFX; AFX1; Afxh; MLLT7; Mllt7; RGD1561201; myeloid/lymphoid or mixed lineage-leukemia translocation to 7 homolog (Drosophila);
Molecular Note Exon 1 was flanked with loxP sites. This is the second major coding exon and encodes the C-terminal half of the full-length protein. [MGI Ref ID J:118179]


Genotyping Information

Genotyping Protocols

Foxo4tm1Rdp, Standard PCR

Helpful Links

Genotyping resources and troubleshooting


References provided by MGI

Selected Reference(s)

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]

Additional References

Foxo4tm1Rdp 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]

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]

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]

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]

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]

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]

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]

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]

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]

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]

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 & HusbandryFoxo4 is X-linked. When maintaining a live colony, homozygous females may be bred to heterozygous males.
Mating SystemHeterozygote (F) x Hemizygote         (Female x Male)   21-APR-14

Pricing and Purchasing

Pricing, Supply Level & Notes, Controls


This strain is currently Under Development - Now Accepting Orders.
Estimated Available for Distribution Date: 22-DEC-14

Please note: You may now place orders for this strain although it is not yet ready for distribution. Estimated available for distribution dates are provided to keep customers better informed on strains under development. Please note that our Colony Managers routinely monitor the target date and edit it based on breeding performance and other factors. The length of time it takes to make a new strain available for distribution depends on genotype, age, number of animals sent by the Donating Investigator, breeding performance, additional strain development (backcrossing, making homozygous), and anticipated demand for the strain.

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

Live Mice

Price per mouse (US dollars $)GenderGenotypes Provided
Individual Mouse $232.00MaleHemizygous for Foxo4tm1Rdp  
$232.00FemaleHeterozygous for Foxo4tm1Rdp  
Individual Mouse $232.00FemaleHomozygous for Foxo4tm1Rdp  
Price per Pair (US dollars $)Pair Genotype
$464.00Heterozygous for Foxo4tm1Rdp x Hemizygous for Foxo4tm1Rdp  
$464.00Homozygous for Foxo4tm1Rdp x Hemizygous for Foxo4tm1Rdp  

Standard Supply

Under Development - Now Accepting Orders The strain development process (i.e. importation, rederivation, and colony expansion) usually takes six to nine months.

Pricing for International shipping destinations View USA Canada and Mexico Pricing

Live Mice

Price per mouse (US dollars $)GenderGenotypes Provided
Individual Mouse $301.60MaleHemizygous for Foxo4tm1Rdp  
$301.60FemaleHeterozygous for Foxo4tm1Rdp  
Individual Mouse $301.60FemaleHomozygous for Foxo4tm1Rdp  
Price per Pair (US dollars $)Pair Genotype
$603.20Heterozygous for Foxo4tm1Rdp x Hemizygous for Foxo4tm1Rdp  
$603.20Homozygous for Foxo4tm1Rdp x Hemizygous for Foxo4tm1Rdp  

Standard Supply

Under Development - Now Accepting Orders The strain development process (i.e. importation, rederivation, and colony expansion) usually takes six to nine months.

View USA Canada and Mexico Pricing View International Pricing

Standard Supply

Under Development - Now Accepting Orders The strain development process (i.e. importation, rederivation, and colony expansion) usually takes six to nine months.

Control Information

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

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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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