Overview

Also Known As: Foxp3^YFP-cre

Foxp3^YFP/cre mutant mice express a knocked-in yellow fluorescent protein/iCre-recombinase fusion protein from the Foxp3 locus without disrupting expression of the endogenous Foxp3 gene. These mice may be useful for studying regulatory T cells suppression of autoimmunity and immune dysfunction.

Donating Investigator

Alexander Rudensky, Memorial Sloan Kettering Cancer Center

Genetic overview

Genetic Background	Generation
	N8+pN2F2 (2019-03-01 00:00:00)

Foxp3^{tm4(YFP/icre)Ayr}

Allele Type	Gene Symbol	Gene Name
Targeted (Recombinase-expressing)	Foxp3	forkhead box P3

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Research Applications

Research Tools
Immunology, Inflammation and Autoimmunity Research

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Base Price

Starting at:

$0.00 Domestic price for male 4-week

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Details

Detailed Description

Foxp3^YFP/cre mutant mice contain an internal ribosome entry site (IRES) and a yellow fluorescent protein (YFP) fused to a codon optimized Cre Recombinase (iCre) sequence downstream of the internal stop codon of the forkhead box P3 (Foxp3) gene. FOXP3 is a transcription factor required for the development and function of regulatory T (T _reg) cells, which regulate suppression of self-reactive T cells. In these mice, YFP expression is evident in FOXP3⁺ T_reg cells. Homozygous females and hemizygous males are viable, fertile and normal in size. When bred with mice containing a loxP-flanked sequence, 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 a floxed-interleukin 10 allele, deletion of IL10 in T _reg cells results in spontaneous colitis, and immune-mediated inflammation in the lungs and skin.

Development

The Foxp3^YFP/cre targeting vector was designed with an internal ribosome entry site (IRES), and a yellow fluorescent protein (YFP) fused to a codon optimized Cre Recombinase (iCre) sequence, followed by a frt-flanked neomycin (neo) resistance cassette 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. The donating investigator reported that these mice were then backcrossed to C57BL/6J mice for at least 8 generations (see SNP note below). Upon arrival at The Jackson Laboratory, mice were bred to C57BL/6J inbred mice (Stock No. 000664) for at least one 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. While the 27 markers throughout the genome suggested a C57BL/6 genetic background, 4 markers that determine C57BL/6J from C57BL/6N were found to be segregating. These data suggest the mice sent to The Jackson Laboratory Repository were on a C57BL/6 ; C57BL/6N mixed genetic background.

Expression Data

Expressed Gene	YFP, Yellow Fluorescent Protein, jellyfish
Expressed Gene	cre, cre recombinase, bacteriophage P1
Site of Expression	YFP florescence is detected in regulatory T cells.

Control Suggestions

Approximate Controls

000664 C57BL/6J

Additional Information

Considerations for Choosing Controls

Selected References

Rubtsov YP; Rasmussen JP; Chi EY; Fontenot J; Castelli L; Ye X; Treuting P; Siewe L; Roers A; Henderson WR Jr; Muller W; Rudensky AY. 2008. Regulatory T cell-derived interleukin-10 limits inflammation at environmental interfaces. Immunity 28(4):546-58PubMed: 18387831 MGI: J:134513

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Genetics

Foxp3^{tm4(YFP/icre)Ayr}

Allele Symbol: Foxp3^{tm4(YFP/icre)Ayr}

Allele Name	targeted mutation 4, Alexander Y Rudensky
Allele Type	Targeted (Recombinase-expressing)
Allele Synonym(s)	targeted mutation 4, Alexander Y Rudensky; Foxp3^{tm4(YFP/icre)Ayr}
Gene Symbol and Name	Foxp3, forkhead box P3
Gene Synonym(s)	AIID; sf; DIETER; IPEX; PIDX; scurfin; XPID; JM2; scurfy; RGD1562112
Expressed Gene	YFP, Yellow Fluorescent Protein, jellyfish
Expressed Gene	cre, cre recombinase, bacteriophage P1
Site of Expression	YFP florescence is detected in regulatory T cells.
Strain of Origin	(129X1/SvJ x 129S1/Sv)F1-Kitl⁺
Chromosome	X
Molecular Note	A YFP/icre fusion construct with an upstream IRES element and a downstream frt-flanked neomycin resistance cassette was placed into the downstream untranslated region of the gene. Chimeric mice were crossed with FLPe expressing mice to remove the neomycin selection cassette. YFP-cre expression based on YFP flouresecene was only detected in regulatory T cells. Crossing these mice with mice that contain a cre-mediated reporter gene also demonstrated low level cre expression in about 2-10% of hematopoietic lineage cells including immature and mature B cells, T cells, myeloid cells and bone marrow precursor cells.
Mutations Made By	Alexander Rudensky, Memorial Sloan Kettering Cancer Center

Disease/Phenotype

Disease Terms

Research Areas By Genotype

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

Research Tools
- Genetics Research
  - Tissue/Cell Markers
- Fluorescent Proteins
Immunology, Inflammation and Autoimmunity Research
- Lymphoid Tissue Defects
- Autoimmunity
- Immunodeficiency
- Inflammation

Mammalian Phenotype Terms by Genotype

References

Rubtsov YP; Rasmussen JP; Chi EY; Fontenot J; Castelli L; Ye X; Treuting P; Siewe L; Roers A; Henderson WR Jr; Muller W; Rudensky AY. 2008. Regulatory T cell-derived interleukin-10 limits inflammation at environmental interfaces. Immunity 28(4):546-58PubMed: 18387831 MGI: J:134513

Additional References

Ameri AH; Moradi Tuchayi S; Zaalberg A; Park JH; Ngo KH; Li T; Lopez E; Colonna M; Lee RT; Mino-Kenudson M; Demehri S. 2019. IL-33/regulatory T cell axis triggers the development of a tumor-promoting immune environment in chronic inflammation. Proc Natl Acad Sci U S A 116(7):2646-2651PubMed: 30696763 MGI: J:271502
Ding Y; Yu A; Tsokos GC; Malek TR. 2019. CD25 and Protein Phosphatase 2A Cooperate to Enhance IL-2R Signaling in Human Regulatory T Cells. J Immunol 203(1):93-104PubMed: 31085588 MGI: J:276865

Additional - Foxp3^{tm4(YFP/icre)Ayr} related

Technical Support

Contact Technical Support

Genotyping Protocols
- Separated PCR:Foxp3^{tm4(YFP/cre)Ayr}
- Genotyping resources and troubleshooting
Breeding Considerations

When maintaining a live colony, homozygous females may be bred to hemizygous males.
- Additional Breeding and Husbandry Support
Mating System
- Homozygote x Hemizygote
Citation
When using the Foxp3^YFP-cre mouse strain in a publication, please cite the originating article(s) and include JAX stock #016959 in your Materials and Methods section.

Animal Health Reports

Facility Barrier Level Descriptions

AX18 (Maximum)

Pricing & Availability

Available

Domestic
International

Live Mouse

Age

Genotype

Price

weeks

Cryorecovery - Not-For-Profit & Academic Pricing

Service	Genotype	Price
	X linked - Heterozygous females and wildtype males for

We will fulfill your order by providing at least two carriers for each strain ordered. The total number, sex, and genotypes provided will vary, although typically 8 or more animals are provided. Please check genotypes which will be recovered. While the genotypes of all animals produced will be communicated to you prior to scheduling shipment, the genotypes of animals provided may not reflect the mating scheme and genotypes described in the strain description. Animals are typically ready to ship in 11-14 weeks. If a second recovery is required to produce the minimum number of animals, then delivery time would increase to approximately 25 weeks. If we fail to produce animals of the correct genotype, you will not be charged. We cannot guarantee the reproductive success of mice shipped to your facility. If the mice are lost after the first three days (post-arrival) or do not produce progeny at your facility, a new order and fee will be necessary.

Cryorecovery to establish a Dedicated Supply for greater quantities of mice. Mice recovered can be used to establish a dedicated colony to contractually supply you mice according to your requirements. Price by quotation.

Related Products and Services

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Frozen Mouse Embryo	B6.129(Cg)-Foxp3<tm4(YFP/icre)Ayr>/J Frozen Embryo	$3373.50
Frozen Mouse Embryo	B6.129(Cg)-Foxp3<tm4(YFP/icre)Ayr>/J Frozen Embryo	$3373.50

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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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Also Known As: Foxp3YFP-cre

Donating Investigator

Genetic overview

Research Applications

Base Price

Detailed Description

Development

Expression Data

Control Suggestions

Approximate Controls

Additional Information

Selected References

Foxp3tm4(YFP/icre)Ayr

Allele Symbol: Foxp3tm4(YFP/icre)Ayr

Disease Terms

Research Areas By Genotype

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

Mammalian Phenotype Terms by Genotype

References

Additional References

Additional - Foxp3tm4(YFP/icre)Ayr related

Genotyping Protocols

Breeding Considerations

Mating System

Citation

Animal Health Reports

Live Mouse

Cryorecovery - Not-For-Profit & Academic Pricing

Related Products and Services

Payment Terms and Conditions

The Jackson Laboratory's Genotype Promise

Terms of Use

Additional Use Restrictions Apply

Licensing Information

JAX® Mice, Products & Services Conditions of Use

No Warranty

Credit for PRODUCTS or SERVICES

Animal Care and Use for SERVICES

No Liability

Also Known As: Foxp3^YFP-cre

Foxp3^{tm4(YFP/icre)Ayr}

Allele Symbol: Foxp3^{tm4(YFP/icre)Ayr}

Additional - Foxp3^{tm4(YFP/icre)Ayr} related