Strain Name:
STOCK Foxp3tm4(icre)Tch/Mmjax
Stock Number:
069553-JAX
Citation ID:
RRID:MMRRC_069553-JAX
Other Names:
Foxp3ΔEGFPiCre (B6.129(Cg)-Foxp3tm4(EGFP/icre)Tch)

Strain Information

Foxp3tm4(EGFP/icre)Tch
Name: forkhead box P3; targeted mutation 4, Talal A Chatila
Synonyms: Foxp3deltaEGFPiCre
Type: Allele
Species: Multi-species
Chromosome: X
Alteration at locus: Knock-In
Foxp3
Name: forkhead box P3
Synonyms: scurfin, JM2
Type: Gene
Species: Mus musculus (mouse)
Chromosome: X
Alteration at locus: Knock-In
NCBI: 20371
HGNC: HGNC:6106
Homologene: 8516
Genetic Alterations
To enable genetic manipulations in ΔTreg cells, we derived a bi-cistronic loss of function Foxp3 allele, Foxp3ΔEGFPiCre, that contained an Frt element inserted between exons 9 and 10 that created an aberrant 3’ splice junction site, leading to a premature stop codon in the Foxp3 transcript. A ribosomal entry sequence inserted in the 3’ untranslated region of Foxp3 directed the expression of a humanized Cre recombinase (iCre) fused with the enhanced green fluorescent protein (EGFP). Treg cells of Foxp3ΔEGFPiCre mice expressed EGFP but not Foxp3. Analysis of Foxp3ΔEGFPiCre mice harboring a Cre-inducible yellow fluorescent protein (YFP) transgene in the Rosa26 locus (R26YFP) revealed that all EGFP+ cells were YFP+ and virtually all within the CD4+ T cell population, indicative of active Cre-mediated excision.
ES Cell Line
SCC10
Phenotype
The mice carry a null Foxp3 allele that directs the expression of an EGFP-Cre recombinase fusion protein. This produces a scurfy phenotype due to impaired regulatory T cell function. The EGFP reporter allows tracking of the mutant regulatory T cell while the Cre recombinase allows mutant Treg cell-specific deletion of floxed genes. These mice are particularly useful in understanding the development of mutant Treg cells due to Foxp3 deficiency and their genetic architecture. They are also useful in testing therapies aimed at correcting the impaired regulatory T cell function due to mutant Foxp3.
Strain Development
The line was developed with SCC10 ES cells derived from 129X1/SvJ. Chimeric males were mated with C57BL6/J females and the PGK-neo cassette was removed by mating to Flp-deleter females (B6.Cg-Tg(ACTFLPe)9205Dym/J, RRID:IMSR_JAX:005703). The mice are maintained as backcrosses to C57BL/6J (males) to heterozygous females without interbreeding due to the X-linked lethal phenotype from immunodysregulation in the mutant males.

Please note that in 2022, a 48 SNP (single nucleotide polymorphism) panel analysis, with 43 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 females sent to The Jackson Laboratory Repository. Three of the 43 markers throughout the genome were segregating with 129, on Chromosomes 3, 6, and 8. Also, one of the 5 markers that determine C57BL/6J from C57BL/6N was found to be segregating, the rd8 recessive mutation associated with retinal degeneration on Chromosome 1 within the Crb1 locus. These data suggest the mice sent to The Jackson Laboratory Repository were of a mixed genetic background.
Suggested Control Mice
C57BL/6J
MMRRC Genetic QC Summary
The MMRRC Centers have developed a genetic QC pipeline using MiniMUGA array genotyping to provide additional information on strain backgrounds for MMRRC congenic and inbred strains. For more information on when data may be available, or to request genotyping for a strain of interest, please contact csmmrrc@jax.org. Older strains may not have this information.
  • Immunology and Inflammation
Donor
Talal Chatila, M.D., Boston Children's Hospital.
Primary Reference

Charbonnier LM, Cui Y, Stephen-Victor E, Harb H, Lopez D, Bleesing JJ, Garcia-Lloret MI, Chen K, Ozen A, Carmeliet P, Li MO, Pellegrini M, Chatila TA. Functional reprogramming of regulatory T cells in the absence of Foxp3. Nat Immunol. 2019 Sep;20(9):1208-1219. doi: 10.1038/s41590-019-0442-x. Epub 2019 Aug 5. (Medline PMCID: 6707855)

Zemmour D, Charbonnier LM, Leon J, Six E, Keles S, Delville M, Benamar M, Baris S, Zuber J, Chen K, Neven B, Garcia-Lloret MI, Ruemmele FM, Brugnara C, Cerf-Bensussan N, Rieux-Laucat F, Cavazzana M, André I, Chatila TA, Mathis D, Benoist C. Single-cell analysis of FOXP3 deficiencies in humans and mice unmasks intrinsic and extrinsic CD4+ T cell perturbations. Nat Immunol. 2021 May;22(5):607-619. doi: 10.1038/s41590-021-00910-8. Epub 2021 Apr 8. (Medline PMCID: 8173714)

Colony and Husbandry Information

Cryo-recovered strains distributed by the MMRRC at JAX are shipped to the customer from the Pathogen & Opportunistic-Free Animal Room G200 - see https://www.jax.org/jax-mice-and-services/customer-support/customer-service/animal-health/health-status-reports.

Mice recovered from a cryo-archive will have health surveillance performed on recipient females. Health reports will be provided prior to shipment. If you require additional health status information, please email csmmrrc@jax.org.
Coat Color
Black
Eye
Pink
MMRRC Breeding System
Backcross
Generation
N8+ (C57BL/6J)
Overall Breeding Performance
Excellent
NOTE: "Hemizygote" as used here refers to males carrying a mutation on the X Chromosome or mice of either sex carrying an inserted transgene with no homologous allele on the other chromosome.
Viability and Fertility: Female Male Comments
Homozygotes are viable: Undetermined X-linked
Homozygotes are fertile: N/A Sterile
Hetero/Hemizygotes are fertile: Yes Sterile
Age Reproductive Decline: Greater than 12 months Undetermined
Average litter size
7 to 9
Recommended wean age
3 Weeks
Average Pups Weaned
7 to 9

Order Request Information

Limited quantities of breeder mice (recovered litter) are available from a cryoarchive; recovered litter usually available to ship in 3 to 4 months.

Cryopreserved material may be available upon request, please inquire to csmmrrc@jax.org for more information.

A Commercial License Agreement from the Donor is required for for-profit entities to use this strain. For more information, please contact Walter Tebbs.

Distribution of this strain requires submission of the MMRRC Conditions of Use (COU). A link to the COU web form will be provided via email after an order has been placed; the form should be completed then or the email forwarded to your institutional official for completion.

A Commercial License Agreement from the Donor is required for for-profit entities to use this strain. For more information, please contact Walter Tebbs

Additional charges may apply for any special requests. Shipping costs are in addition to the basic distribution/resuscitation fees. Information on shipping costs and any additional charges will be provided by the supplying MMRRC facility.

Click button to Request this one strain. (Use the MMRRC Catalog Search to request more than one strain.)
MMRRC Item # Description Distribution Fee / Unit (US $)
*Shipping & Handling not included*
Units Notes
069553-JAX-EMBRYO Cryo-preserved embryos $1,038.00 / $1,038.00
Non-Profit / For-Profit
Aliquot Approximate quantity2 : 20-40 embryos / aliquot
069553-JAX-RESUS Litter recovered from cryo-archive $2,022.00 / $2,022.00
Non-Profit / For-Profit
Litter Recovered litter4; additional fees for any special requests.
Cryopreserved material may be available upon request, please inquire to csmmrrc@jax.org for more information.

1 The distribution fee covers the expense of rederiving mice from a live mouse; you will receive the resulting litter. The litter will contain at minimum one mutant carrier; the actual number of animals and the gender and genotype ratios will vary. (Typically, multiple breeder pairs can be established from the recovered litter.) Prior to shipment, the MMRRC will provide information about the animals recovered. If you anticipate or find that you need to request specific genotypes, genders or quantities of mice in excess of what is likely from a resuscitated litter, you may discuss available options and pricing with the supplying MMRRC facility.

2 An aliquot contains a sufficient number of embryos (in one or more vials or straws and based on the transfer success rate of the MMRRC facility) to transfer into one to three recipients. The MMRRC makes no guarantee concerning embryo transfer success experienced in the recipient investigator's laboratory. Neither gender nor genotype ratios are guaranteed.

3 An aliquot is one straw or vial with sufficient sperm to recover at least one litter of mice, as per provided protocols, when performed at the MMRRC facility. The MMRRC makes no guarantee concerning the success of these procedures when performed outside the MMRRC facilities.

4 The distribution fee covers the expense of resuscitating mice from the cryo-archive; you will receive the resulting litter. The litter will contain at minimum one mutant carrier; the actual number of animals and the gender and genotype ratios will vary. (Typically, multiple breeder pairs can be established from the recovered litter.) Prior to shipment, the MMRRC will provide information about the animals recovered. If you anticipate or find that you need to request specific genotypes, genders or quantities of mice in excess of what is likely from a resuscitated litter, you may discuss available options and pricing with the supplying MMRRC facility.

To request material from the MMRRC: Please fill out our on-line request form (accessible from the catalog search results page, or click the Request this Strain button in the fees section). If you have questions or need assistance completing this form, you may call Customer Service at (800) 910-2291 (in USA or Canada) or (530) 757-5710 (international calls). Before you call, please have with you: the MMRRC item number, quantity needed, Bill-to and Ship-to contact information.