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| This X-linked targeted knock-in strain co-marks cells expressing the Foxp3 (forkhead box P3) gene with monomeric red fluorescent protein (mRFP). RFP expression faithfully marks gene expression in lymphocytes. This strain may be helpful in studies of Foxp3-expressing regulatory T cells. | |||||||||||||||||||
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- Disease & phenotype
- Genes & alleles
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Description
Strain Information
Type Coisogenic; Targeted Mutation; Additional information on Genetically Engineered and Mutant Mice. Visit our online Nomenclature tutorial. Mating System Homozygote x Hemizygote (Female x Male) 19-DEC-08 Species laboratory mouse Generation N11+F8 (29-JUN-11)
Generation DefinitionsDonating Investigator Dr. Richard A. Flavell, Yale University School of Medicine Description
Mice homozygous/hemizygous for this X-linked targeted knock-in are viable and fertile and do not display any gross physical or behavioral abnormalities. Cells expressing the forkhead box P3 gene are co-marked with monomeric red fluorescent protein (mRFP). RFP expression faithfully marks gene expression in lymphocytes. This strain may be helpful in studies of forkhead box P3-expressing regulatory T cells.Development
A targeting construct composed of a IRES-mRFP cassette was linked to a LoxP-flanked neomycin (Neo) selection marker was electroporated into Bruce 4 C57BL/6 embryonic stem (ES) cells. To obtain chimeric mice, ES clones correctly targeted to exon 13 were injected into BALB/c blastocysts, which were then implanted in CD1 pseudopregnant foster mothers. Male chimeras were bred with C57BL/6 to screen for germ-line-transmitted offspring. Germ-line-transmitted mice were bred with Tet-Cre transgenic mice (deleter mice) to remove the neomycin gene. This strain was backcrossed to C57BL/6Ncr (see SNP note below) more than 10 generations by the donating laboratory.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. While the 27 markers throughout the genome suggested a C57BL/6 genetic background, all 5 markers that determine C57BL/6J from C57BL/6N were found to be segregating.
Control Information
| Control | ||
|---|---|---|
| 000664 C57BL/6J | ||
| Considerations for Choosing Controls | ||
Related Strains
Fluorescent Protein Strains
View Fluorescent Protein Strains (357 strains)
016959 B6.129(Cg)-Foxp3tm4(YFP/cre)Ayr/J 004088 B6.Cg-Foxp3sf/J 018628 B6.Cg-Foxp3tm1Mal/J 019933 B6.Cg-Foxp3tm1Tch/J 006772 B6.Cg-Foxp3tm2Tch/J 014579 B6.NOD-Tg(Foxp3-EGFP/cre)1aJbs/J 016958 B6N.129(Cg)-Foxp3tm3Ayr/J 020654 C.129X1-Foxp3tm3Tch/J 021144 C.Cg-Foxp3tm1Tch/J 006769 C.Cg-Foxp3tm2Tch/J 006775 NOD.Cg-Foxp3sf/DoiJ 008694 NOD/ShiLt-Tg(Foxp3-EGFP/cre)1cJbs/J 016961 STOCK Foxp3tm9(EGFP/cre/ERT2)Ayr/J
Additional Web Information
Fluorescent Proteins/lacZ Systems
Phenotype
Phenotype Information
- Potential model based on gene homology relationships. Phenotypic similarity to the human disease has not been tested. Diabetes Mellitus, Insulin-Dependent; IDDM (FOXP3)
Immunodysregulation, Polyendocrinopathy, and Enteropathy, X-Linked; (FOXP3)
assigned by genotype
Foxp3tm1Flv/Foxp3+
involves: C57BL/6
- normal phenotype
- no abnormal phenotype detected
- heterozygotes are fertile, develop normally, and have normal lymphocyte development and function (MGI Ref ID J:97415)
This mouse can be used to support research in many areas including:
Immunology, Inflammation and Autoimmunity Research
Research Tools
Fluorescent Proteins
Genes & Alleles
Gene & Allele Information provided by MGI
| Allele Symbol | Foxp3tm1Flv | ||
|---|---|---|---|
| Allele Name | targeted mutation 1, Richard A Flavell | ||
| Allele Type | Targeted (Reporter) | ||
| Common Name(s) | FIR; Foxp3-IRES-RFP; Foxp3-IRES-mRFP; Foxp3-RFP; | ||
| Mutation Made By | Dr. Richard Flavell, Yale University School of Medicine | ||
| Strain of Origin | B6.Cg-Thy1 | ||
| ES Cell Line Name | Bruce 4 | ||
| ES Cell Line Strain | B6.Cg-Thy1 | ||
| Site of Expression | RFP expression faithfully marks gene expression in lymphocytes. | ||
| Expressed Gene | RFP, Red Fluorescent Protein, coral | ||
| Red Fluorescent Protein (RFP), derived from marine invertebrate organisms such as the soft coral Discosoma spp and reef coral, Heteractis crispa, is a versatile reporter molecule which has found use in many biological applications. The wild type protein, which is an obligate tetramer, is not well tolerated in mammalian systems. The original molecule has been modified in order to optimize expression to mammalian physiology (examples include monomeric RFP, mRFP1, DsRed, etc). | |||
| Molecular Note | A targeting cassette containing an IRES-mRFP and a floxed neo was inserted between the translation stop codon and the polyA signal of the locus. Crossing with cre deleter mice removed the neo. Flow cytometry revealed mRFP expression occurred where Foxp3 is normally expressed. [MGI Ref ID J:97415] | ||
| Gene Symbol and Name | Foxp3, forkhead box P3 | ||
| Chromosome | X | ||
| Gene Common Name(s) | AIID; DIETER; IPEX; JM2; PIDX; RGD1562112; XPID; scurfin; scurfy; sf; | ||
Genotyping
Genotyping Information
Genotyping Protocols
Foxp3tm1Flv, Separated PCR
Helpful Links
Genotyping resources and troubleshooting
References
References provided by MGI
Selected Reference(s)
Wan YY; Flavell RA. 2005. Identifying Foxp3-expressing suppressor T cells with a bicistronic reporter. Proc Natl Acad Sci U S A 102(14):5126-31. [PubMed: 15795373] [MGI Ref ID J:97415]
Additional References
Foxp3tm1Flv relatedBaine I; Basu S; Ames R; Sellers RS; Macian F. 2013. Helios induces epigenetic silencing of IL2 gene expression in regulatory T cells. J Immunol 190(3):1008-16. [PubMed: 23275607] [MGI Ref ID J:193030]
Bayer AL; Chirinos J; Cabello C; Yang J; Matsutani T; Malek TR; Levy RB. 2011. Expansion of a restricted residual host T reg-cell repertoire is dependent on IL-2 following experimental autologous hematopoietic stem transplantation. Eur J Immunol 41(12):3467-78. [PubMed: 21928285] [MGI Ref ID J:179509]
Chae WJ; Gibson TF; Zelterman D; Hao L; Henegariu O; Bothwell AL. 2010. Ablation of IL-17A abrogates progression of spontaneous intestinal tumorigenesis. Proc Natl Acad Sci U S A 107(12):5540-4. [PubMed: 20212110] [MGI Ref ID J:158691]
Cheng G; Yu A; Dee MJ; Malek TR. 2013. IL-2R Signaling Is Essential for Functional Maturation of Regulatory T Cells during Thymic Development. J Immunol 190(4):1567-75. [PubMed: 23315074] [MGI Ref ID J:193324]
Cheng G; Yuan X; Tsai MS; Podack ER; Yu A; Malek TR. 2012. IL-2 receptor signaling is essential for the development of Klrg1+ terminally differentiated T regulatory cells. J Immunol 189(4):1780-91. [PubMed: 22786769] [MGI Ref ID J:189754]
Esplugues E; Huber S; Gagliani N; Hauser AE; Town T; Wan YY; O'Connor W Jr; Rongvaux A; Van Rooijen N; Haberman AM; Iwakura Y; Kuchroo VK; Kolls JK; Bluestone JA; Herold KC; Flavell RA. 2011. Control of TH17 cells occurs in the small intestine. Nature 475(7357):514-8. [PubMed: 21765430] [MGI Ref ID J:174687]
Gutcher I; Donkor MK; Ma Q; Rudensky AY; Flavell RA; Li MO. 2011. Autocrine Transforming Growth Factor-beta1 Promotes In Vivo Th17 Cell Differentiation. Immunity 34(3):396-408. [PubMed: 21435587] [MGI Ref ID J:169839]
Hawiger D; Wan YY; Eynon EE; Flavell RA. 2010. The transcription cofactor Hopx is required for regulatory T cell function in dendritic cell-mediated peripheral T cell unresponsiveness. Nat Immunol 11(10):962-8. [PubMed: 20802482] [MGI Ref ID J:164689]
Hirota K; Turner JE; Villa M; Duarte JH; Demengeot J; Steinmetz OM; Stockinger B. 2013. Plasticity of TH17 cells in Peyer's patches is responsible for the induction of T cell-dependent IgA responses. Nat Immunol 14(4):372-9. [PubMed: 23475182] [MGI Ref ID J:194909]
Huber S; Gagliani N; Esplugues E; O'Connor W Jr; Huber FJ; Chaudhry A; Kamanaka M; Kobayashi Y; Booth CJ; Rudensky AY; Roncarolo MG; Battaglia M; Flavell RA. 2011. Th17 Cells Express Interleukin-10 Receptor and Are Controlled by Foxp3(-) and Foxp3(+) Regulatory CD4(+) T Cells in an Interleukin-10-Dependent Manner. Immunity 34(4):554-65. [PubMed: 21511184] [MGI Ref ID J:171598]
Hurez V; Daniel BJ; Sun L; Liu AJ; Ludwig SM; Kious MJ; Thibodeaux SR; Pandeswara S; Murthy K; Livi CB; Wall S; Brumlik MJ; Shin T; Zhang B; Curiel TJ. 2012. Mitigating age-related immune dysfunction heightens the efficacy of tumor immunotherapy in aged mice. Cancer Res 72(8):2089-99. [PubMed: 22496463] [MGI Ref ID J:185818]
Kamanaka M; Huber S; Zenewicz LA; Gagliani N; Rathinam C; O'Connor W Jr; Wan YY; Nakae S; Iwakura Y; Hao L; Flavell RA. 2011. Memory/effector (CD45RB(lo)) CD4 T cells are controlled directly by IL-10 and cause IL-22-dependent intestinal pathology. J Exp Med 208(5):1027-40. [PubMed: 21518800] [MGI Ref ID J:177300]
Kamanaka M; Kim ST; Wan YY; Sutterwala FS; Lara-Tejero M; Galan JE; Harhaj E; Flavell RA. 2006. Expression of interleukin-10 in intestinal lymphocytes detected by an interleukin-10 reporter knockin tiger mouse. Immunity 25(6):941-52. [PubMed: 17137799] [MGI Ref ID J:116616]
Khan SQ; Tsai MS; Schreiber TH; Wolf D; Deyev VV; Podack ER. 2013. Cloning, Expression, and Functional Characterization of TL1A-Ig. J Immunol 190(4):1540-50. [PubMed: 23319737] [MGI Ref ID J:193316]
Kriegel MA; Rathinam C; Flavell RA. 2009. E3 ubiquitin ligase GRAIL controls primary T cell activation and oral tolerance. Proc Natl Acad Sci U S A 106(39):16770-5. [PubMed: 19805371] [MGI Ref ID J:153216]
Li MO; Wan YY; Flavell RA. 2007. T cell-produced transforming growth factor-beta1 controls T cell tolerance and regulates Th1- and Th17-cell differentiation. Immunity 26(5):579-91. [PubMed: 17481928] [MGI Ref ID J:123547]
Lin PY; Sun L; Thibodeaux SR; Ludwig SM; Vadlamudi RK; Hurez VJ; Bahar R; Kious MJ; Livi CB; Wall SR; Chen L; Zhang B; Shin T; Curiel TJ. 2010. B7-H1-dependent sex-related differences in tumor immunity and immunotherapy responses. J Immunol 185(5):2747-53. [PubMed: 20686128] [MGI Ref ID J:163243]
Long M; Park SG; Strickland I; Hayden MS; Ghosh S. 2009. Nuclear factor-kappaB modulates regulatory T cell development by directly regulating expression of Foxp3 transcription factor. Immunity 31(6):921-31. [PubMed: 20064449] [MGI Ref ID J:156178]
Meng X; Zhang Y; Jia Z; Huo X; He X; Tian G; Wu M; Wang Z; Zhou X; Xiong S; Gao X; Wu Z; Han J; Zhao L; Wang P; Hong Z; Wang Q; Yin Z. 2013. A novel tylophorine analog W-8 up-regulates forkhead boxP3 expression and ameliorates murine colitis. J Leukoc Biol 93(1):83-93. [PubMed: 23142729] [MGI Ref ID J:193745]
Miska J; Bas E; Devarajan P; Chen Z. 2012. Autoimmunity-mediated antitumor immunity: Tumor as an immunoprivileged self. Eur J Immunol 42(10):2584-96. [PubMed: 22777737] [MGI Ref ID J:188006]
Molinero LL; Miller ML; Evaristo C; Alegre ML. 2011. High TCR stimuli prevent induced regulatory T cell differentiation in a NF-kappaB-dependent manner. J Immunol 186(8):4609-17. [PubMed: 21411734] [MGI Ref ID J:172516]
Ouyang W; Beckett O; Flavell RA; Li MO. 2009. An essential role of the Forkhead-box transcription factor Foxo1 in control of T cell homeostasis and tolerance. Immunity 30(3):358-71. [PubMed: 19285438] [MGI Ref ID J:147057]
Ouyang W; Beckett O; Ma Q; Li MO. 2010. Transforming growth factor-beta signaling curbs thymic negative selection promoting regulatory T cell development. Immunity 32(5):642-53. [PubMed: 20471291] [MGI Ref ID J:160693]
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]
Ouyang W; Liao W; Luo CT; Yin N; Huse M; Kim MV; Peng M; Chan P; Ma Q; Mo Y; Meijer D; Zhao K; Rudensky AY; Atwal G; Zhang MQ; Li MO. 2012. Novel Foxo1-dependent transcriptional programs control T(reg) cell function. Nature 491(7425):554-9. [PubMed: 23135404] [MGI Ref ID J:189962]
Reis BS; Rogoz A; Costa-Pinto FA; Taniuchi I; Mucida D. 2013. Mutual expression of the transcription factors Runx3 and ThPOK regulates intestinal CD4(+) T cell immunity. Nat Immunol 14(3):271-80. [PubMed: 23334789] [MGI Ref ID J:193391]
Schreiber TH; Wolf D; Tsai MS; Chirinos J; Deyev VV; Gonzalez L; Malek TR; Levy RB; Podack ER. 2010. Therapeutic Treg expansion in mice by TNFRSF25 prevents allergic lung inflammation. J Clin Invest 120(10):3629-40. [PubMed: 20890040] [MGI Ref ID J:165331]
Sela U; Olds P; Park A; Schlesinger SJ; Steinman RM. 2011. Dendritic cells induce antigen-specific regulatory T cells that prevent graft versus host disease and persist in mice. J Exp Med 208(12):2489-96. [PubMed: 22084406] [MGI Ref ID J:178615]
Tsiperson V; Gruber RC; Goldberg MF; Jordan A; Weinger JG; Macian F; Shafit-Zagardo B. 2013. Suppression of Inflammatory Responses during Myelin Oligodendrocyte Glycoprotein-Induced Experimental Autoimmune Encephalomyelitis Is Regulated by AKT3 Signaling. J Immunol 190(4):1528-39. [PubMed: 23335751] [MGI Ref ID J:193496]
Turnquist HR; Zhao Z; Rosborough BR; Liu Q; Castellaneta A; Isse K; Wang Z; Lang M; Stolz DB; Zheng XX; Demetris AJ; Liew FY; Wood KJ; Thomson AW. 2011. IL-33 expands suppressive CD11b+ Gr-1 int and regulatory T cells, including ST2L+ Foxp3+ cells, and mediates regulatory T cell-dependent promotion of cardiac allograft survival. J Immunol 187(9):4598-610. [PubMed: 21949025] [MGI Ref ID J:179437]
Wan YY; Flavell RA. 2007. Regulatory T-cell functions are subverted and converted owing to attenuated Foxp3 expression. Nature 445(7129):766-70. [PubMed: 17220876] [MGI Ref ID J:118631]
Wang Y; Souabni A; Flavell RA; Wan YY. 2010. An intrinsic mechanism predisposes foxp3-expressing regulatory T cells to th2 conversion in vivo. J Immunol 185(10):5983-92. [PubMed: 20944002] [MGI Ref ID J:165629]
Wei G; Abraham BJ; Yagi R; Jothi R; Cui K; Sharma S; Narlikar L; Northrup DL; Tang Q; Paul WE; Zhu J; Zhao K. 2011. Genome-wide analyses of transcription factor GATA3-mediated gene regulation in distinct T cell types. Immunity 35(2):299-311. [PubMed: 21867929] [MGI Ref ID J:176231]
Xiang Y; Peng J; Tai N; Hu C; Zhou Z; Wong FS; Wen L. 2012. The dual effects of B cell depletion on antigen-specific T cells in BDC2.5NOD mice. J Immunol 188(10):4747-58. [PubMed: 22490442] [MGI Ref ID J:188690]
Yamazaki S; Bonito AJ; Spisek R; Dhodapkar M; Inaba K; Steinman RM. 2007. Dendritic cells are specialized accessory cells along with TGF- for the differentiation of Foxp3+ CD4+ regulatory T cells from peripheral Foxp3 precursors. Blood 110(13):4293-302. [PubMed: 17699744] [MGI Ref ID J:149108]
Health & husbandry
Health & Colony Maintenance Information
Animal Health Reports
Room Number AX11
Colony Maintenance
Breeding & Husbandry When maintained as a live colony, homozygous females may be bred with hemizygous males. This mutation is X-linked. Mating System Homozygote x Hemizygote (Female x Male) 19-DEC-08 Diet Information LabDiet® 5K52/5K67
Pricing and Purchasing
Pricing, Supply Level & Notes, Controls
| Pricing for USA, Canada and Mexico shipping destinations |
|
Live Mice
Price per mouse (US dollars $) Gender Genotypes Provided Individual Mouse $177.00 Male Hemizygous for Foxp3tm1Flv $177.00 Female Homozygous for Foxp3tm1Flv
Price per Pair (US dollars $) Pair Genotype $354.00 Homozygous for Foxp3tm1Flv x Hemizygous for Foxp3tm1Flv Standard Supply
Repository-Live. Repository-Live represents an exclusive set of over 1500 unique mouse models maintained at The Jackson Laboratory to support a vast array of research areas. The breeding colonies for Repository Strains provide mice for both large and small orders and fluctuate in size depending on current demand for each strain. Repository-live orders are treated as custom orders. Within 2 business days, we respond to each availability inquiry or order with various delivery options. Repository Strains typically are delivered at 4 to 8 weeks of age and will not exceed 12 weeks of age on the day of shipping.
| Pricing for International shipping destinations |
|
Live Mice
Price per mouse (US dollars $) Gender Genotypes Provided Individual Mouse $230.10 Male Hemizygous for Foxp3tm1Flv $230.10 Female Homozygous for Foxp3tm1Flv
Price per Pair (US dollars $) Pair Genotype $460.20 Homozygous for Foxp3tm1Flv x Hemizygous for Foxp3tm1Flv Standard Supply
Repository-Live. Repository-Live represents an exclusive set of over 1500 unique mouse models maintained at The Jackson Laboratory to support a vast array of research areas. The breeding colonies for Repository Strains provide mice for both large and small orders and fluctuate in size depending on current demand for each strain. Repository-live orders are treated as custom orders. Within 2 business days, we respond to each availability inquiry or order with various delivery options. Repository Strains typically are delivered at 4 to 8 weeks of age and will not exceed 12 weeks of age on the day of shipping.
|
|
|
Standard Supply
Repository-Live. Repository-Live represents an exclusive set of over 1500 unique mouse models maintained at The Jackson Laboratory to support a vast array of research areas. The breeding colonies for Repository Strains provide mice for both large and small orders and fluctuate in size depending on current demand for each strain. Repository-live orders are treated as custom orders. Within 2 business days, we respond to each availability inquiry or order with various delivery options. Repository Strains typically are delivered at 4 to 8 weeks of age and will not exceed 12 weeks of age on the day of shipping.
Control Information
| Control | ||
|---|---|---|
| 000664 C57BL/6J | ||
| 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.Ordering Information
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