C57BL/6-Tg(Foxp3-DTR/EGFP)23.2Spar/Mmjax

MMRRC Stock No:: 32050-JAX |; DEREG

Available

Overview

Also Known As: DEREG

These "depletion of regulatory T cell" (DEREG) BAC transgenic mice express a simian diphtheria toxin receptor-enhanced green fluorescent protein (DTR-eGFP) fusion protein under control of the endogenous forkhead box P3 promoter/enhancer regions on the BAC transgene. DTR-eGFP expression is observed in fully functional Foxp3⁺CD4⁺ regulatory T cell populations allowing fluorescent detection or diphtheria toxin-induced ablation Foxp3⁺ T reg cells.

Donating Investigator

Tim Sparwasser, University Medical Center of the Johannes Gutenberg University Mainz

Genetic overview

Genetic Background	Generation
	?+pN3F9 (2019-01-25 00:00:00)

Tg(Foxp3-DTR/EGFP)23.2Spar

Allele Type
Transgenic (Inserted expressed sequence)

View Genetics

Research Applications

Research Tools
Immunology, Inflammation and Autoimmunity Research
Internal/Organ Research

View All Research Applications

Details

Detailed Description

Mice hemizygous for the "depletion of regulatory T cell" (DEREG) BAC transgene are viable and fertile, with expression of a simian diphtheria toxin receptor-enhanced green fluorescent protein (DTR-eGFP) fusion protein under control of the endogenous Foxp3 (forkhead box P3) promoter/enhancer regions on the BAC transgene. The donating investigator reports that transcription/translation from the BAC Foxp3 locus is disabled. These DEREG mice have DTR-eGFP expression in fully functional Foxp3⁺CD4⁺ regulatory T cell populations with no observed influence on regulation of the endogenous Foxp3 locus. Specifically, EGFP expression (via FACS) is observed mainly in CD25⁺CD4⁺ T cells, and allows specific detection of Foxp3⁺ regulatory T cell populations. The donating investigator also reports that EGFP expression is measurable by direct fluorescence. Diphtheria toxin (DT) administration results in ablation of Foxp3⁺CD4⁺ T reg cells with no apparent affect on CD25⁺ effector T cells. DT-induced depletion of Foxp3⁺CD4⁺ T reg cells is associated with enhanced and prolonged delayed-type hypersensitivity (DTH) responses and neonatal development of scurfy-like symptoms. The donating investigator reports that while homozygous females breed fine, homozygous males seem infertile.

Development

The RP23-267C15 bacterial artificial chromosome (BAC) containing at least ten mouse genes was obtained. This BAC was modified by targeting a simian diphtheria toxin receptor-enhanced green fluorescent protein (DTR-eGFP) fusion protein and an SV40 polyA element into the first exon of the Foxp3 (forkhead box P3) locus: none of the other loci on the BAC were mutated. This modified ~150 kb BAC transgene was microinjected into the pronuclei of fertilized C57BL/6NCrl oocytes. Transgenic mice were identified and bred to C57BL/6J wildtype mice to establish the high transgene expressing founder line 23.2. These "depletion of regulatory T cell" (DEREG) mice were subsequently maintained by breeding transgenic mice with wildtype C57BL/6J or wildtype siblings for many generations prior to arrival at The Jackson Laboratory. Upon arrival, mice were bred to C57BL/6J inbred mice for at least one generation to establish the colony.

Expression Data

Expressed Gene	DTR, Simian Diphtheria Toxin Receptor,
Expressed Gene	GFP, Green Fluorescent Protein,
Site of Expression	Selective DTR-eGFP expression is seen within the CD4+ T cell compartment, and highest expression within the CD25+ subset.

Control Suggestions

Noncarrier
000664 C57BL/6J

Additional Information

Considerations for Choosing Controls

Selected References

Lahl K; Loddenkemper C; Drouin C; Freyer J; Arnason J; Eberl G; Hamann A; Wagner H; Huehn J; Sparwasser T. 2007. Selective depletion of Foxp3+ regulatory T cells induces a scurfy-like disease. J Exp Med 204(1):57-63PubMed: 17200412 MGI: J:125295
Jung S; Unutmaz D; Wong P; Sano G; De los Santos K; Sparwasser T; Wu S; Vuthoori S; Ko K; Zavala F; Pamer EG; Littman DR; Lang RA. 2002. In vivo depletion of CD11c(+) dendritic cells abrogates priming of CD8(+) T cells by exogenous cell-associated antigens. Immunity 17(2):211-20PubMed: 12196292 MGI: J:93488

View All References

Genetics

Tg(Foxp3-DTR/EGFP)23.2Spar

Allele Symbol: Tg(Foxp3-DTR/EGFP)23.2Spar

Allele Name	transgene insertion 23.2, Tim Sparwasser
Allele Type	Transgenic (Inserted expressed sequence)
Allele Synonym(s)	transgene insertion 23.2, Tim Sparwasser; Tg(Foxp3-DTR/EGFP)23.2Spar
Gene Symbol and Name	Tg(Foxp3-DTR/EGFP)23.2Spar, transgene insertion 23.2, Tim Sparwasser
Gene Synonym(s)
Promoter	Foxp3, forkhead box P3, mouse, laboratory
Expressed Gene	DTR, Simian Diphtheria Toxin Receptor,
Expressed Gene	GFP, Green Fluorescent Protein,
Site of Expression	Selective DTR-eGFP expression is seen within the CD4+ T cell compartment, and highest expression within the CD25+ subset.
Strain of Origin	C57BL/6NCrl
Chromosome	UN
Molecular Note	The RP23-267C15 bacterial artificial chromosome (BAC) containing at least ten mouse genes was obtained. This BAC was modified by targeting a simian diphtheria toxin receptor-enhanced green fluorescent protein (DTR-eGFP) fusion protein and an SV40 polyA element into the first exon of the Foxp3 (forkhead box P3) locus: none of the other loci on the BAC were mutated. Two high expressing lines (16.1 and 23.2) were established. Analysis revealed selective DTR-eGFP expression within the CD4+ T cell compartment, with the highest expression within the CD25+ subset.
Mutations Made By	Tim Sparwasser, Twincore Inst. for Infection Immunology

Disease/Phenotype

Disease Terms

Research Areas By Genotype

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

Research Tools
- Immunology, Inflammation and Autoimmunity Research
  - specific T cell deficiency
  - T cell deficiency
  - production of T cell lines and hybridomas
  - T cell specific surface marker
- Genetics Research
  - Tissue/Cell Markers
  - Tissue/Cell Markers: T cell specific surface marker
- Cancer Research
  - production of T cells and hybridoma
  - specific T cell deficiency
  - T cell deficiency
- Fluorescent Proteins
Immunology, Inflammation and Autoimmunity Research
- CD Antigens, Antigen Receptors, and Histocompatibility Markers
  - genes regulating susceptibility to infectious disease and endotoxin
- Immunodeficiency
  - T cell deficiency
  - specific T cell deficiency
- Autoimmunity
- Intracellular Signaling Molecules
- Inflammation
Internal/Organ Research
- Lymphoid Tissue Defects
  - T cell deficiency

Mammalian Phenotype Terms by Genotype

The following phenotype relates to a compound genotype created using this strain

Genotype: Tg(Foxp3-DTR/EGFP)23.2Spar/0
involves: C57BL/6NCrl

endocrine/exocrine gland phenotype

insulitis
- following diphtheria toxin treatment of neonates, mice exhibit insulitis and portal aggregates unlike similarly treated wild-type mice

integument phenotype

epidermal hyperplasia
- following diphtheria toxin treatment of neonates, the skin overlying the hyaline cartilage of the ear is thickened with epidermal hyperplasia and a dense lymphocyte infiltrate unlike in similarly treated wild-type mice

skin inflammation
- following diphtheria toxin treatment of neonates, the skin overlying the hyaline cartilage of the ear is thickened with epidermal hyperplasia and a dense lymphocyte infiltrate unlike in similarly treated wild-type mice

hematopoietic system phenotype

decreased regulatory T cell number
- following diphtheria toxin treatment, CD4+ T regulatory cells are decreased in adult and neonates compared to in similarly treated wild-type mice
- Normal - however, T regulatory cell numbers rebound after cessation of diphtheria treatment in adult mice but not neonates

enlarged spleen
- following diphtheria toxin treatment of neonates

increased spleen red pulp amount
- following diphtheria toxin treatment of neonates

increased spleen white pulp amount
- following diphtheria toxin treatment of neonates

mammalian phenotype

immune system phenotype
- Normal - mice exhibit normal numbers and frequencies of CD25+CD4+ T regulatory cells

respiratory system phenotype

abnormal pulmonary alveolus morphology
- following diphtheria toxin treatment of neonates, alveoli are delicate and have thin walls compared to in similarly treated wild-type mice

lung inflammation
- following diphtheria toxin treatment of neonates, mice exhibit peribronchial and perivascular infiltrated unlike similarly treated wild-type mice

immune system phenotype

decreased regulatory T cell number
- following diphtheria toxin treatment, CD4+ T regulatory cells are decreased in adult and neonates compared to in similarly treated wild-type mice
- Normal - however, T regulatory cell numbers rebound after cessation of diphtheria treatment in adult mice but not neonates

enlarged lymph nodes
- following diphtheria toxin treatment of neonates

enlarged spleen
- following diphtheria toxin treatment of neonates

increased inflammatory response
- diphtheria toxin treated-neonates exhibit massive inflammatory infiltrate in various organs that resembles the phenotype of Foxp3^sf hemizygotes

increased spleen red pulp amount
- following diphtheria toxin treatment of neonates

increased spleen white pulp amount
- following diphtheria toxin treatment of neonates

increased susceptibility to type IV hypersensitivity reaction
- following diphtheria toxin treatment, adult mice exhibit an enhanced and prolonged delayed-type hypersensitivity response compared with similarly treated wild-type mice

insulitis
- following diphtheria toxin treatment of neonates, mice exhibit insulitis and portal aggregates unlike similarly treated wild-type mice

lung inflammation
- following diphtheria toxin treatment of neonates, mice exhibit peribronchial and perivascular infiltrated unlike similarly treated wild-type mice

lymph node hyperplasia
- following diphtheria toxin treatment of neonates

skin inflammation
- following diphtheria toxin treatment of neonates, the skin overlying the hyaline cartilage of the ear is thickened with epidermal hyperplasia and a dense lymphocyte infiltrate unlike in similarly treated wild-type mice

References

Lahl K; Loddenkemper C; Drouin C; Freyer J; Arnason J; Eberl G; Hamann A; Wagner H; Huehn J; Sparwasser T. 2007. Selective depletion of Foxp3+ regulatory T cells induces a scurfy-like disease. J Exp Med 204(1):57-63PubMed: 17200412 MGI: J:125295
Jung S; Unutmaz D; Wong P; Sano G; De los Santos K; Sparwasser T; Wu S; Vuthoori S; Ko K; Zavala F; Pamer EG; Littman DR; Lang RA. 2002. In vivo depletion of CD11c(+) dendritic cells abrogates priming of CD8(+) T cells by exogenous cell-associated antigens. Immunity 17(2):211-20PubMed: 12196292 MGI: J:93488

Additional - Tg(Foxp3-DTR/EGFP)23.2Spar related

Technical Support

Contact Technical Support

Genotyping Protocols
- QPCR:Generic GFP
- Standard PCR:Tg(Foxp3-DTR/EGFP)23.2Spar
- Standard PCR:Tg(Foxp3-DTR/EGFP)23.2Spar
- Genotyping resources and troubleshooting
Dietary Information
- LabDiet® 5K52 formulation (6% fat)
Breeding Considerations

When maintaining a live colony, hemizygous mice may be bred to wildtype (noncarrier) siblings or to C57BL/6J inbred mice (Stock No. 000664). The donating investigator reports that while homozygous females breed fine, homozygous males seem infertile.
- Additional Breeding and Husbandry Support
Mating System
- Noncarrier x Hemizygote
- Hemizygote x Noncarrier
Citation
When using the DEREG mouse strain in a publication, please cite the originating article(s) and include MMRRC stock #32050 in your Materials and Methods section.

Animal Health Reports

Facility Barrier Level Descriptions

AX18 (Maximum)

The Jackson Laboratory's Genotype Promise

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.

Terms Of Use

Terms of Use

General Terms and Conditions

Questions about Terms of Use

Licensing Information

Phone: 207-288-6470

Email: TechTran@jax.org

JAX® Mice, Products & Services Conditions of Use

"MICE" means mouse strains, their progeny derived by inbreeding or crossbreeding, unmodified derivatives from mouse strains or their progeny supplied by The Jackson Laboratory ("JACKSON"). "PRODUCT(S)" means biological materials supplied by JACKSON, and their derivatives. "SERVICES" means projects conducted by JACKSON for other parties that may include but are not limited to the use of MICE or PRODUCTS. "RECIPIENT" means each recipient of MICE, PRODUCTS, or SERVICES provided by JACKSON including each institution, its employees and other researchers under its control. MICE or PRODUCTS shall not be: (i) used for any purpose other than internal research, (ii) sold or otherwise provided to any third party for any use, or (iii) provided to any agent or other third party to provide breeding or other services. Acceptance of MICE, PRODUCTS or SERVICES from JACKSON shall be deemed as agreement by RECIPIENT to these conditions, and departure from these conditions requires JACKSON’s prior written authorization.

No Warranty

MICE, PRODUCTS AND SERVICES ARE PROVIDED "AS IS". JACKSON EXTENDS NO WARRANTIES OF ANY KIND, EITHER EXPRESS, IMPLIED, OR STATUTORY, WITH RESPECT TO MICE, PRODUCTS OR SERVICES, INCLUDING ANY IMPLIED WARRANTY OF MERCHANTABILITY OR FITNESS FOR A PARTICULAR PURPOSE, OR ANY WARRANTY OF NON-INFRINGEMENT OF ANY PATENT, TRADEMARK, OR OTHER INTELLECTUAL PROPERTY RIGHTS.

Credit for PRODUCTS or SERVICES

In case of dissatisfaction for a valid reason and claimed in writing by a purchaser within ninety (90) days of receipt of, PRODUCTS or SERVICES, JACKSON will, at its option, provide credit or replacement for the PRODUCT received or the SERVICES provided; JACKSON makes no other representations and this shall be the exclusive remedy of the purchaser. Please note specific policy for live mice.

Animal Care and Use for SERVICES

Consistent with the requirement for a written understanding regarding animal care and use, the JACKSON Animal Care and Use Committee will review the animal care and use protocol(s) associated with any SERVICES to be performed at JACKSON, and JACKSON shall have ultimate responsibility and authority for the care of animals while on site or in JACKSON custody.

No Liability

In no event shall JACKSON, its trustees, directors, officers, employees, and affiliates be liable for any causes of action or damages, including any direct, indirect, special, or consequential damages, arising out of the provision of MICE, PRODUCTS, or SERVICES, including economic damage or injury to property and lost profits, and including any damage arising from acts or negligence on the part of JACKSON, its agents or employees. Unless prohibited by law, in purchasing or receiving MICE, PRODUCTS, or SERVICES from JACKSON, purchaser or recipient, or any party claiming by or through them, expressly releases and discharges JACKSON from all such causes of action or damages, and further agrees to defend and indemnify JACKSON from any costs or damages arising out of any third party claims.

MICE, PRODUCTS or SERVICES are to be used in a safe manner and in accordance with all applicable governmental rules and regulations.

The foregoing represents the General Terms and Conditions applicable to JACKSON’s MICE, PRODUCTS or SERVICES. In addition, special terms and conditions of sale of certain MICE, PRODUCTS, or SERVICES may be set forth separately in JACKSON web pages, catalogs, price lists, contracts, and/or other documents, and these special terms and conditions shall also govern the sale of these MICE, PRODUCTS and SERVICES by JACKSON, and by its licensees and distributors.

Acceptance of delivery of MICE, PRODUCTS or SERVICES shall be deemed agreement to these terms and conditions. No purchase order or other document transmitted by purchaser or recipient that may modify the terms and conditions hereof, shall be in any way binding on JACKSON, and instead the terms and conditions set forth herein, including any special terms and conditions set forth separately, shall govern the sale of MICE, PRODUCTS or SERVICES by JACKSON.

Also Known As: DEREG

Donating Investigator

Genetic overview

Research Applications

Detailed Description

Development

Expression Data

Control Suggestions

Additional Information

Selected References

Tg(Foxp3-DTR/EGFP)23.2Spar

Allele Symbol: Tg(Foxp3-DTR/EGFP)23.2Spar

Disease Terms

Research Areas By Genotype

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

Mammalian Phenotype Terms by Genotype

Genotype: Tg(Foxp3-DTR/EGFP)23.2Spar/0involves: C57BL/6NCrl

endocrine/exocrine gland phenotype

integument phenotype

hematopoietic system phenotype

mammalian phenotype

respiratory system phenotype

immune system phenotype

References

Additional - Tg(Foxp3-DTR/EGFP)23.2Spar related

Genotyping Protocols

Dietary Information

Breeding Considerations

Mating System

Citation

Animal Health Reports

The Jackson Laboratory's Genotype Promise

Terms of Use

Licensing Information

JAX® Mice, Products & Services Conditions of Use

No Warranty

Credit for PRODUCTS or SERVICES

Animal Care and Use for SERVICES

No Liability

Genotype: Tg(Foxp3-DTR/EGFP)23.2Spar/0
involves: C57BL/6NCrl