Overview

Also Known As: Foxp3^K276X BALB/c

These Foxp3^K276X (forkhead box P3) mutant mice exhibit multisystem lymphoproliferative and myeloproliferative disease, and have applications in studies of T regulatory (Treg) cell function and allergic inflammation.

Donating Investigator

Talal Chatila, Boston Children's Hospital

Genetic overview

Genetic Background	Generation

Foxp3^tm1Tch

Allele Type	Gene Symbol	Gene Name
Targeted (Null/Knockout)	Foxp3	forkhead box P3

View Genetics

Research Applications

Immunology, Inflammation and Autoimmunity Research
Developmental Biology Research
Hematological Research
Internal/Organ Research
Research Tools

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Base Price

Starting at:

$2,854.50 Domestic price Cryo Recovery

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Details

Detailed Description

The transcriptional regulator FOXP3 is in the forkhead/winged-helix family and is important in T regulatory cells (Tregs) development and function. These mice carry a targeted mutation of the Foxp3 gene that contains the K276X nonsense mutation (A to T substitution in the first base position of codon 276) in exon 8, which creates a stop codon. Female mice that are heterozygous for the mutation are viable and fertile. Male mice carrying this X-linked mutation die within a few weeks after birth, due to aggressive lymphoproliferative and myeloproliferative disease. No gene product (mRNA or protein) is detected by Real-time PCR or FACS analysis of mutant splenocytes. Null mice exhibit decreased numbers of B cells. By 2 weeks of age, mutant male mice exhibit spontaneous allergic airway inflammation, progressive lymphoproliferation and myeloproliferation and blood eosinophilia. Male hemizygotes on a congenic C57BL/6 background live longer (up to 60 days) than male hemizygotes on a BALB/c background (up to 23 days).

Development

A targeting vector designed by Dr. Talal A. Chatila (UCLA) containing a loxP flanked NEO cassette was used to introduce the K276X nonsense mutation (A to T substitution in the first base position of codon 276) in exon 8, creating a stop codon. The construct was electroporated into 129X1/SvJ derived RW4 embryonic stem (ES) cells. Correctly targeted ES cells were injected into C57BL/6 blastocysts. The resulting chimeric male animals were crossed to BALB/c female mice. The mice were then crossed to EIIa-cre deleter mice on a mixed BALB/c, C57BL/6 background to remove the floxed NEO cassette. The mice were then backcrossed to BALB/c for 15 generations. Upon arrival at The Jackson Laboratory, the mice were crossed to BALB/cJ
(Stock No. 000651) at least once to establish the colony.

Control Suggestions

000651 BALB/cJ

Additional Information

Considerations for Choosing Controls

Selected References

Lin W; Truong N; Grossman WJ; Haribhai D; Williams CB; Wang J; Martin MG; Chatila TA. 2005. Allergic dysregulation and hyperimmunoglobulinemia E in Foxp3 mutant mice. J Allergy Clin Immunol 116(5):1106-15PubMed: 16275384 MGI: J:117165

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Genetics

Foxp3^tm1Tch

Allele Symbol: Foxp3^tm1Tch

Allele Name	targeted mutation 1, Talal A Chatila
Allele Type	Targeted (Null/Knockout)
Allele Synonym(s)	Foxp3^tm1Tch; targeted mutation 1, Talal A Chatila
Gene Symbol and Name	Foxp3, forkhead box P3
Gene Synonym(s)	AIID; sf; DIETER; IPEX; PIDX; scurfin; XPID; JM2; scurfy; RGD1562112
Strain of Origin	129X1/SvJ
Chromosome	X
Molecular Note	A vector was designed to change codon K276 to a stop codon in exon 8. A neo included in the vector was subsequently removed via cre mediated recombination.

Disease/Phenotype

Disease Terms

Research Areas By Genotype

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

Immunology, Inflammation and Autoimmunity Research
- Inflammation
- Lymphoid Tissue Defects
  - hematopoietic development
- Immunodeficiency
  - T cell deficiency
Developmental Biology Research
- Lymphoid Tissue Defects
  - hematopoietic defects
Hematological Research
- Hematopoietic Defects
- Immunological Defects
Internal/Organ Research
- Lymphoid Tissue Defects
  - T cell deficiency
Research Tools
- Immunology, Inflammation and Autoimmunity Research
  - T cell deficiency
- Hematological Research

Mammalian Phenotype Terms by Genotype

The following phenotype information is associated with a similar, but not exact match to this JAX^® Mice strain

Genotype: Foxp3^tm1Tch/Y
B6.129X1-Foxp3

hematopoietic system phenotype

anemia

increased eosinophil cell number
- marked blood eosinophilia

increased IgE level
- at 23 to 30 days of age, IgE levels are increased by about 4 orders of magnitude compared to littermate controls
- hyperimmunoglobulinemia E

increased leukocyte cell number

increased lymphocyte cell number
- lymphocytosis

increased monocyte cell number
- monocytosis

thrombocytopenia

integument phenotype

dermatitis
- prominent

mortality/aging

postnatal lethality, complete penetrance
- Background Sensitivity - survival is longer than in mice on a BALB/c background

respiratory system phenotype

respiratory system inflammation
- allergic airway inflammation found at 2 weeks of age
- inflammation includes peribronchial infiltrates, goblet cell metaplasia, and mucus impaction

immune system phenotype

abnormal inflammatory response
- multisystem lymphoproliferative and myeloproliferative disease similar to mice on a BALB/c background

dermatitis
- prominent

increased eosinophil cell number
- marked blood eosinophilia

increased IgE level
- at 23 to 30 days of age, IgE levels are increased by about 4 orders of magnitude compared to littermate controls
- hyperimmunoglobulinemia E

increased leukocyte cell number

increased lymphocyte cell number
- lymphocytosis

increased monocyte cell number
- monocytosis

respiratory system inflammation
- allergic airway inflammation found at 2 weeks of age
- inflammation includes peribronchial infiltrates, goblet cell metaplasia, and mucus impaction

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

Genotype: Foxp3^tm1Tch/Foxp3⁺
C.129X1-Foxp3

normal phenotype

no abnormal phenotype detected
- Normal - viable and fertile with no signs of lymphoproliferative disorders

Genotype: Foxp3^tm1Tch/Y
C.129X1-Foxp3

digestive/alimentary phenotype

crypts of Lieberkuhn abscesses
- seen at 2 weeks of age

homeostasis/metabolism phenotype

abnormal chemokine level
- elevated levels of chemotactic factor monocyte chemotactic protein 1

increased circulating interferon-gamma level
- elevated levels of IFNG

increased circulating interleukin-10 level
- elevated levels of IL-10

increased circulating interleukin-4 level
- elevated levels of IL-4

increased circulating interleukin-5 level
- elevated levels of IL-5

increased circulating interleukin-6 level
- elevated levels of IL-6

increased circulating tumor necrosis factor level
- elevated levels of TNFA

endocrine/exocrine gland phenotype

crypts of Lieberkuhn abscesses
- seen at 2 weeks of age

immune system phenotype

abnormal chemokine level
- elevated levels of chemotactic factor monocyte chemotactic protein 1

abnormal cytokine secretion
- nonselective dysregulated production of both Th1 and Th2 cytokines

abnormal inflammatory response
- an eosinophilic and neutrophilic infiltration is found in the gastrointestinal tract
- mixed inflammatory infiltrate containing lymphocytes, neutrophils, monocytes, and eosinophils is found in the liver, stomach, pancreas, and skin

abnormal lymphocyte physiology
- at 2 weeks of age mice display an intense lymphoproliferative and myeloproliferative disorder

absent regulatory T cells
- absence of CD4+ CD25+ regulatory T cells

dermatitis
- prominent

enlarged spleen
- massive splenomegaly at 2 weeks of age

increased activated T cell number
- significant proportion of CD4+ and CD8+ cell populations are activated

increased CD4-positive, alpha beta T cell number
- marked expansion of CD4+ cell populations

increased CD8-positive, alpha-beta T cell number
- marked expansion of CD8+ cell populations

increased circulating interferon-gamma level
- elevated levels of IFNG

increased circulating interleukin-10 level
- elevated levels of IL-10

increased circulating interleukin-4 level
- elevated levels of IL-4

increased circulating interleukin-5 level
- elevated levels of IL-5

increased circulating interleukin-6 level
- elevated levels of IL-6

increased circulating tumor necrosis factor level
- elevated levels of TNFA

increased eosinophil cell number
- marked blood eosinophilia

increased IgE level
- hyperimmunoglobulinemia E

increased IgG1 level
- striking increase in IgG1

increased leukocyte cell number

increased lymphocyte cell number
- lymphocytosis

increased monocyte cell number
- monocytosis

respiratory system inflammation
- allergic airway inflammation found at 2 weeks of age
- inflammation includes peribronchial infiltrates, goblet cell metaplasia, and mucus impaction

hematopoietic system phenotype

abnormal lymphocyte physiology
- at 2 weeks of age mice display an intense lymphoproliferative and myeloproliferative disorder

absent regulatory T cells
- absence of CD4+ CD25+ regulatory T cells

anemia

enlarged spleen
- massive splenomegaly at 2 weeks of age

increased activated T cell number
- significant proportion of CD4+ and CD8+ cell populations are activated

increased CD4-positive, alpha beta T cell number
- marked expansion of CD4+ cell populations

increased CD8-positive, alpha-beta T cell number
- marked expansion of CD8+ cell populations

increased eosinophil cell number
- marked blood eosinophilia

increased IgE level
- hyperimmunoglobulinemia E

increased IgG1 level
- striking increase in IgG1

increased leukocyte cell number

increased lymphocyte cell number
- lymphocytosis

increased monocyte cell number
- monocytosis

thrombocytopenia

integument phenotype

dermatitis
- prominent

mortality/aging

postnatal lethality, complete penetrance
- hemizygous males develop lymphoproliferative disease with median survival of ~15 days of age, similar to Foxp3^tm3Tch males
- median survival is 16.5 days
- Background Sensitivity - survival is shorter than in mice on a C57BL/6 background

respiratory system phenotype

abnormal respiratory mucosa goblet cell morphology
- goblet cell metaplasia in the lungs

respiratory system inflammation
- allergic airway inflammation found at 2 weeks of age
- inflammation includes peribronchial infiltrates, goblet cell metaplasia, and mucus impaction

References

Lin W; Truong N; Grossman WJ; Haribhai D; Williams CB; Wang J; Martin MG; Chatila TA. 2005. Allergic dysregulation and hyperimmunoglobulinemia E in Foxp3 mutant mice. J Allergy Clin Immunol 116(5):1106-15PubMed: 16275384 MGI: J:117165

Additional - Foxp3^tm1Tch related

Technical Support

Contact Technical Support

Genotyping Protocols
- Standard PCR:Foxp3^tm1Tch
- Standard PCR:Foxp3^tm1Tch
- Genotyping resources and troubleshooting
Breeding Considerations

When maintaining a live colony, female mice can be bred as heterozygotes. Male mice carrying this X-linked mutation die within a few weeks after birth, due to aggressive lymphoproliferative and myeloproliferative disease.
- Additional Breeding and Husbandry Support
Citation
When using the Foxp3^K276X BALB/c mouse strain in a publication, please cite the originating article(s) and include JAX stock #021144 in your Materials and Methods section.

Animal Health Reports

Facility Barrier Level Descriptions

Production of mice from cryopreserved embryos or sperm occurs in a maximum barrier room, G200

Pricing & Availability

Cryo Recovery

Domestic
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Live Mouse

Age

Genotype

Price

weeks

Cryorecovery - Pricing

Service	Genotype	Price
	H Linked -Heterozygous females and Non carrier males

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

Frozen Mouse Embryo	C.Cg-Foxp3<tm1Tch>/J	$2595.00
Frozen Mouse Embryo	C.Cg-Foxp3<tm1Tch>/J	$2595.00
Frozen Mouse Embryo	C.Cg-Foxp3<tm1Tch>/J	$3373.50
Frozen Mouse Embryo	C.Cg-Foxp3<tm1Tch>/J	$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: Foxp3K276X BALB/c

Donating Investigator

Genetic overview

Research Applications

Base Price

Detailed Description

Development

Control Suggestions

Additional Information

Selected References

Foxp3tm1Tch

Allele Symbol: Foxp3tm1Tch

Disease Terms

Research Areas By Genotype

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

Mammalian Phenotype Terms by Genotype

Genotype: Foxp3tm1Tch/YB6.129X1-Foxp3

hematopoietic system phenotype

integument phenotype

mortality/aging

respiratory system phenotype

immune system phenotype

Genotype: Foxp3tm1Tch/Foxp3+C.129X1-Foxp3

normal phenotype

Genotype: Foxp3tm1Tch/YC.129X1-Foxp3

digestive/alimentary phenotype

homeostasis/metabolism phenotype

endocrine/exocrine gland phenotype

immune system phenotype

hematopoietic system phenotype

integument phenotype

mortality/aging

respiratory system phenotype

References

Additional - Foxp3tm1Tch related

Genotyping Protocols

Breeding Considerations

Citation

Animal Health Reports

Production of mice from cryopreserved embryos or sperm occurs in a maximum barrier room, G200

Live Mouse

Cryorecovery - 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^K276X BALB/c

Foxp3^tm1Tch

Allele Symbol: Foxp3^tm1Tch

Genotype: Foxp3^tm1Tch/Y
B6.129X1-Foxp3

Genotype: Foxp3^tm1Tch/Foxp3⁺
C.129X1-Foxp3

Genotype: Foxp3^tm1Tch/Y
C.129X1-Foxp3

Additional - Foxp3^tm1Tch related