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| Foxp3EGFP-cre-ERT2 mutant mice contain an internal ribosome entry site (IRES) and an enhanced green fluorescent protein (EGFP) fused to a CreERT2 fusion gene downstream of the internal stop codon of the forkhead box P3 (Foxp3) gene. These mice may be useful for studying lineage stability and genetic mapping of regulatory T cells. | |||||||||||||||||||||||||||
- Description
- Disease & phenotype
- Genes & alleles
- Genotyping
- Health & care
- References
- Pricing & purchasing
- Terms of use
Description
Strain Information
Type Mutant Stock; Targeted Mutation; Additional information on Genetically Engineered and Mutant Mice. Visit our online Nomenclature tutorial. Mating System Heterozygote x Hemizygote (Female x Male) 27-MAR-13 Species laboratory mouse Generation N3+pN1 (22-MAR-13)
Generation DefinitionsDonating Investigator Alexander Rudensky, University of Washington Description
Foxp3EGFP-cre-ERT2 mutant mice contain an internal ribosome entry site (IRES) and an enhanced green fluorescent protein (EGFP) fused to a CreERT2 fusion gene (Cre recombinase fused to a G400V/M543A/L544A triple mutation of the human estrogen receptor ligand binding domain) downstream of the internal stop codon of the forkhead box P3 (Foxp3) gene. Homozygous females and hemizygous males are viable, fertile, and normal in size. FOXP3 is a transcription factor required for the development and function of regulatory T (T reg) cells, which are required for suppression of self-reactive T cells and prevention of some autoimmune diseases. In these mice, EGFP expression is evident in FOXP3+ Treg cells. Cre-ERT2 fusion gene activity is inducible; observed in the same cells only following tamoxifen administration. When Foxp3EGFP-cre-ERT2 mice are bred with mice containing loxP-flanked sequence, tamoxifen-inducible, Cre-mediated recombination will result in deletion of the floxed sequences in T reg cells of the offspring. For example, when these mice are bred with mice containing the Gt(ROSA)26Sortm1(EYFP)Cos allele, deletion of the floxed-STOP cassette in T reg cells results in 3 populations of CD4+ cells: unlabeled FOXP3- cells, EGFP+ YFP- FOXP3- cells, and EGFP+ YFP+ FOXP3- cells. These mice may be useful for studying lineage stability and genetic mapping of regulatory T cells.The Cre-ERT2 fusion protein consists of Cre recombinase fused to a triple mutant form of the human estrogen receptor which does not bind its natural ligand (17β-estradiol) at physiological concentrations but will bind the synthetic estrogen receptor ligands 4-hydroxytamoxifen (OHT or tamoxifen) and, with lesser sensitivity, ICI 182780. Restricted to the cytoplasm, Cre-ERT2 can only gain access to the nuclear compartment after exposure to tamoxifen. To counteract the mixed estrogen agonist effects of tamoxifen injections, which can result in late fetal abortions in pregnant mice, progesterone may be coadministered.
Development
The Foxp3EGFP-cre-ERT2 targeting vector was designed with an internal ribosome entry site (IRES), and an enhanced green fluorescent protein (EGFP) fused to a CreERT2 fusion gene (Cre recombinase fused to a G400V/M543A/L544A triple mutation of the human estrogen receptor ligand binding domain), followed by a frt-flanked neomycin (neo) resistance cassette. This construct was inserted downstream of the internal stop codon of the X-linked forkhead box P3 (Foxp3) gene. This construct was injected into (129X1/SvJ x 129S1/Sv)F1-Kitl+-derived R1 embryonic stem (ES) cells. Correctly targeted ES cells were injected into C57BL/6 blastocysts, and the resulting chimeric males were bred to FLP-deleter mice (on a B6 background) to remove the neo cassette. These mice were then backcrossed to C57BL/6J mice for at least 3 generations. Upon arrival at The Jackson Laboratory, mice were bred to C57BL/6J inbred mice (Stock No. 000664) for at least one generation.
Control Information
| Control | ||
|---|---|---|
| 000664 C57BL/6J | (approximate) | |
| Considerations for Choosing Controls | ||
Related Strains
Strains carrying other alleles of Foxp3
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 008374 C57BL/6-Foxp3tm1Flv/J 006775 NOD.Cg-Foxp3sf/DoiJ 008694 NOD/ShiLt-Tg(Foxp3-EGFP/cre)1cJbs/J View Strains carrying other alleles of Foxp3 (13 strains)
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
The following phenotype information may relate to a genetic background differing from this JAX® Mice strain.
Foxp3tm9(EGFP/cre/ERT2)Ayr/Y
Background Not Specified
- no phenotypic analysis
- *normal* no phenotypic analysis
- no details of analysis are provided; mice are used in various genetic crosses (MGI Ref ID J:171734)
This mouse can be used to support research in many areas including:
GFP relatedImmunology, Inflammation and Autoimmunity Research
Autoimmunity
Immunodeficiency
Inflammation
Lymphoid Tissue Defects
Research Tools
Fluorescent Proteins
Genetics Research
Tissue/Cell Markers
cre relatedResearch Tools
Fluorescent Proteins
Cre-lox System
Genetics Research
Mutagenesis and Transgenesis
Mutagenesis and Transgenesis: Cre-lox System
Genes & Alleles
Gene & Allele Information provided by MGI
| Allele Symbol | Foxp3tm9(EGFP/cre/ERT2)Ayr | ||
|---|---|---|---|
| Allele Name | targeted mutation 9, Alexander Y Rudensky | ||
| Allele Type | Targeted (knock-in) | ||
| Common Name(s) | Foxp3-GFP-Cre; Foxp3eGFP-Cre-ERT2; | ||
| Mutation Made By | Alexander Rudensky, University of Washington | ||
| Site of Expression | Expression is seen in regulatory T cells. | ||
| Expressed Gene | cre, cre recombinase, bacteriophage P1 | ||
| Cre recombinase is an enzyme derived from the bacteriophage P1 that specifically recognizes loxP sites. Cre has been shown to effectively mediate the excision of DNA located between loxP sites. After the excision event, the DNA ends recombine leaving a single loxP site in place of the intervening sequence. | |||
| Expressed Gene | GFP, Green Fluorescent Protein, jellyfish | ||
| Green Fluorescent Protein (GFP), derived from the jellyfish Aequorea victoria, is a versatile reporter molecule which has found use in many biological applications. In some constructs the original molecule has been modified in order to enhance its fluorescence intensity (EGFP, enhanced GFP). When utilized in a transgenic construct, tissue expressing sufficient amounts of GFP will fluoresce when exposed to a 488 nm light source. | |||
| Driver Note | Foxp3 | ||
| Inducible Note | induced by tamoxifen | ||
| Molecular Note | An IRES element followed by an EGFP-cre-ERT2 coding sequence was knocked into the 3' UTR of the Foxp3 locus. [MGI Ref ID J:171734] | ||
| Gene Symbol and Name | Foxp3, forkhead box P3 | ||
| Chromosome | X | ||
| Gene Common Name(s) | AIID; DIETER; IPEX; JM2; PIDX; XPID; scurfin; scurfy; sf; | ||
Genotyping
Genotyping Information
Genotyping Protocols
Foxp3tm9(EGFP/cre/ERT2)AyrAlternate2,SEPARATED MELT
gT(ROSA)26Sortm1(EYFP)Cos/J MCA SEP, Melt Curve Analysis
Helpful Links
Genotyping resources and troubleshooting
References
References provided by MGI
Selected Reference(s)
Rubtsov YP; Niec RE; Josefowicz S; Li L; Darce J; Mathis D; Benoist C; Rudensky AY. 2010. Stability of the regulatory T cell lineage in vivo. Science 329(5999):1667-71. [PubMed: 20929851] [MGI Ref ID J:171734]
Additional References
Foxp3tm9(EGFP/cre/ERT2)Ayr relatedChaudhry A; Samstein RM; Treuting P; Liang Y; Pils MC; Heinrich JM; Jack RS; Wunderlich FT; Bruning JC; Muller W; Rudensky AY. 2011. Interleukin-10 signaling in regulatory T cells is required for suppression of th17 cell-mediated inflammation. Immunity 34(4):566-78. [PubMed: 21511185] [MGI Ref ID J:171597]
Josefowicz SZ; Niec RE; Kim HY; Treuting P; Chinen T; Zheng Y; Umetsu DT; Rudensky AY. 2012. Extrathymically generated regulatory T cells control mucosal TH2 inflammation. Nature 482(7385):395-9. [PubMed: 22318520] [MGI Ref ID J:181322]
Yadav M; Louvet C; Davini D; Gardner JM; Martinez-Llordella M; Bailey-Bucktrout S; Anthony BA; Sverdrup FM; Head R; Kuster DJ; Ruminski P; Weiss D; Von Schack D; Bluestone JA. 2012. Neuropilin-1 distinguishes natural and inducible regulatory T cells among regulatory T cell subsets in vivo. J Exp Med 209(10):1713-22, S1-19. [PubMed: 22966003] [MGI Ref ID J:191422]
Health & husbandry
Health & Colony Maintenance Information
Animal Health Reports
Room Number AX18
Colony Maintenance
Breeding & Husbandry When maintaining a live colony, homozygous females may be bred to hemizygous males. Mating System Heterozygote x Hemizygote (Female x Male) 27-MAR-13 Diet Information LabDiet® 5K52/5K67
Pricing and Purchasing
Pricing, Supply Level & Notes, Controls
This strain is currently Under Development - Now Accepting Orders.
Estimated Available for Distribution Date:
15-JUL-13
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 |
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Live Mice
Price per mouse (US dollars $) Gender Genotypes Provided Individual Mouse $232.00 Male Hemizygous for Foxp3tm9(EGFP/cre/ERT2)Ayr $232.00 Female Heterozygous for Foxp3tm9(EGFP/cre/ERT2)Ayr Individual Mouse $232.00 Female Homozygous for Foxp3tm9(EGFP/cre/ERT2)Ayr
Price per Pair (US dollars $) Pair Genotype $464.00 Heterozygous for Foxp3tm9(EGFP/cre/ERT2)Ayr x Hemizygous for Foxp3tm9(EGFP/cre/ERT2)Ayr $464.00 Homozygous for Foxp3tm9(EGFP/cre/ERT2)Ayr x Hemizygous for Foxp3tm9(EGFP/cre/ERT2)Ayr 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 |
|
Live Mice
Price per mouse (US dollars $) Gender Genotypes Provided Individual Mouse $301.60 Male Hemizygous for Foxp3tm9(EGFP/cre/ERT2)Ayr $301.60 Female Heterozygous for Foxp3tm9(EGFP/cre/ERT2)Ayr Individual Mouse $301.60 Female Homozygous for Foxp3tm9(EGFP/cre/ERT2)Ayr
Price per Pair (US dollars $) Pair Genotype $603.20 Heterozygous for Foxp3tm9(EGFP/cre/ERT2)Ayr x Hemizygous for Foxp3tm9(EGFP/cre/ERT2)Ayr $603.20 Homozygous for Foxp3tm9(EGFP/cre/ERT2)Ayr x Hemizygous for Foxp3tm9(EGFP/cre/ERT2)Ayr Standard Supply
Under Development - Now Accepting Orders The strain development process (i.e. importation, rederivation, and colony expansion) usually takes six to nine months.
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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
| Control | ||
|---|---|---|
| 000664 C57BL/6J | (approximate) | |
| Considerations for Choosing Controls | ||
| Control Pricing Information for Genetically Engineered Mutant Strains. | ||
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