Overview

These IL4Rα Y500F mutant mice may be useful in immunological studies of mitogenic signal transduction in response to IL-4, specifically antigen-specific antibody responses, allergic airway inflammation, and asthma.

Donating Investigator

Talal Chatila, Boston Children's Hospital

Genetic overview

Genetic Background	Generation

Il4ra^tm1Tch

Allele Type	Gene Symbol	Gene Name
Targeted (Inserted expressed sequence)	Il4ra	interleukin 4 receptor, alpha

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Research Applications

Immunology, Inflammation and Autoimmunity Research
Internal/Organ Research
Cell Biology Research
Hematological Research
Research Tools
Diabetes and Obesity Research

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Base Price

Starting at:

$2,854.50 Domestic price Cryo Recovery

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Details

Detailed Description

Mice homozygous for this "IL4Rα Y500F" mutant allele are viable and fertile. The mice express a mutant IL4Rα chain with a phenylalanine substitution at the proximal tyrosine residue (Y500F) in the cytoplasmic tail. This residue is a critical component of the insulin/interleukin-4 receptor (I4R) motif, and is required for binding by phosphotyrosine-binding domain (PTB) adaptor proteins and for initiating subsequent downstream signaling cascades in response to IL-4. Allele-specific PCR verifies the amino acid substitution. The Y500F mutation abrogates insulin receptor substrate-2 (IRS-2) phosphorylation, and impairs IL-4-induced CD4+ lymphocyte proliferation with no reported effect on Stat6 activation, IL-4-responsive gene product up-regulation, or Th cell differentiation under Th2 polarizing conditions. In vivo, the Y500F mutation is associated with increased allergen-induced IgE production, airway hyper-responsiveness (AHR), tissue eosinophilia, goblet cell metaplasia, and mucus production. These IL4Rα Y500F mutant mice may be useful in immunological studies of mitogenic signal transduction in response to IL-4, specifically antigen-specific antibody responses, allergic airway inflammation, and asthma.

Development

The targeting vector was designed (by site-directed mutagenesis) to change an adenine to thymidine at basepair 1735 of the murine IL-4Rα cDNA sequence, resulting in a corresponding single amino acid substitution of tyrosine to phenylalanine at codon 500 (Y500F). A loxp-flanked PGK-neo cassette was also inserted within intron 11. The construct was electroporated into 129X1/SvJ-derived RW4 embryonic stem (ES) cells. Correctly targeted ES cells were transiently transfected with a cre-expressing vector to remove the selection cassette (leaving a single loxp site in intron 11) and then injected into C57BL/6 blastocysts. The resulting chimeric males were crossed to BALB/c females. Heterozygotes were bred to BALB/c for 12 generations prior to arrival at The Jackson Laboratory.

Control Suggestions

Approximate Controls

Additional Information

Considerations for Choosing Controls

Selected References

Blaeser F; Bryce PJ; Ho N; Raman V; Dedeoglu F; Donaldson DD; Geha RS; Oettgen HC; Chatila TA. 2003. Targeted inactivation of the IL-4 receptor alpha chain I4R motif promotes allergic airway inflammation. J Exp Med 198(8):1189-200PubMed: 14557412 MGI: J:86215

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Genetics

Il4ra^tm1Tch

Allele Symbol: Il4ra^tm1Tch

Allele Name	targeted mutation 1, Talal A Chatila
Allele Type	Targeted (Inserted expressed sequence)
Allele Synonym(s)	Y500F
Gene Symbol and Name	Il4ra, interleukin 4 receptor, alpha
Gene Synonym(s)
Promoter	Il4ra, interleukin 4 receptor, alpha, mouse, laboratory
Strain of Origin	129X1/SvJ
Chromosome	7
Molecular Note	A single A to T substitution was created at the position equivalent to 1735 of the cDNA. This caused a codon change for amino acid residue 500 from tyrosine to phenylalanine (Y500F) disrupting the PTB domain. In addition, a floxed PGK-neomycin resistance cassette was inserted into intron 11. This cassette was removed from successfully targeted clones by transient transfection with a Cre recombinase. The mutant is transcribed at rates equivalent to those of wild-type as indicated by RT-PCR.
Mutations Made By	Talal Chatila, Boston Children's Hospital

Disease/Phenotype

Disease Terms

Model with phenotypic similarity to human disease where etiologies are distinct. Human genes are associated with this disease. Orthologs of these genes do not appear in the mouse genotype(s).

asthma

Research Areas By Phenotype

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

Immunology, Inflammation and Autoimmunity Research
- Immunodeficiency
  - Asthma
  - multiple immune defects
  - T cell deficiency
- Inflammation
  - Asthma
- Lymphoid Tissue Defects
- Intracellular Signaling Molecules
- Growth Factors/Receptors/Cytokines
- Autoimmunity
Internal/Organ Research
- Lymphoid Tissue Defects
Cell Biology Research
- Signal Transduction
Hematological Research
- Immunological Defects
Research Tools
- Cell Biology Research
- Hematological Research
- Immunology, Inflammation and Autoimmunity Research
  - T cell deficiency
Diabetes and Obesity Research
- Insulin Receptors and Growth Factors

Mammalian Phenotype Terms by Genotype

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

Genotype: Il4ra^tm1Tch/Il4ra^tm1Tch
involves: 129X1/SvJ * BALB/c

cellular phenotype

decreased T cell proliferation
- impaired Il-4 induced CD4⁺ T cell proliferation

respiratory system phenotype

increased airway responsiveness
- with methacholine challenge

respiratory system inflammation
- airway hyperresponsiveness to methacholine
- eosinophilic infiltration
- goblet cell hyperplasia

hematopoietic system phenotype

abnormal T-helper 2 cell morphology
- decreased persistence of Th2 cells as indicated by Il-4, Il-5, and Il-13 production
- Th2 differentiation not impaired however

decreased T cell proliferation
- impaired Il-4 induced CD4⁺ T cell proliferation

increased IgE level
- levels are substantially higher than normal

increased IgG level
- IgG1 and IgG2 levels are higher than normal in response to OVA stimulation

immune system phenotype

abnormal immune serum protein physiology

abnormal T-helper 2 cell morphology
- decreased persistence of Th2 cells as indicated by Il-4, Il-5, and Il-13 production
- Th2 differentiation not impaired however

decreased T cell proliferation
- impaired Il-4 induced CD4⁺ T cell proliferation

increased IgE level
- levels are substantially higher than normal

increased IgG level
- IgG1 and IgG2 levels are higher than normal in response to OVA stimulation

respiratory system inflammation
- airway hyperresponsiveness to methacholine
- eosinophilic infiltration
- goblet cell hyperplasia

References

Blaeser F; Bryce PJ; Ho N; Raman V; Dedeoglu F; Donaldson DD; Geha RS; Oettgen HC; Chatila TA. 2003. Targeted inactivation of the IL-4 receptor alpha chain I4R motif promotes allergic airway inflammation. J Exp Med 198(8):1189-200PubMed: 14557412 MGI: J:86215

Additional - Il4ra^tm1Tch related

Technical Support

CONTACT TECHNICAL SUPPORT

Genotyping Protocols
- Pyrosequencing:Il4ra
- Genotyping resources and troubleshooting
Breeding Considerations

When maintaining a live colony, these mice may be bred as homozygotes.
- Additional Breeding and Husbandry Support
Citation
When using the C.129X1-Il4ra^tm1Tch/J mouse strain in a publication, please cite the originating article(s) and include JAX stock #007680 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
International

Live Mouse

Age

Genotype

Price

weeks

Cryorecovery - Pricing

Service/Product	Description	Price
	Heterozygous for Il4ra<tm1Tch>

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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. We do not guarantee breeding performance and therefore suggest that investigators order more than one breeding pair to avoid delays in their research.

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Donating Investigator

Genetic overview

Research Applications

Base Price

Detailed Description

Development

Control Suggestions

Approximate Controls

Additional Information

Selected References

Il4ratm1Tch

Allele Symbol: Il4ratm1Tch

Disease Terms

Model with phenotypic similarity to human disease where etiologies are distinct. Human genes are associated with this disease. Orthologs of these genes do not appear in the mouse genotype(s).

Research Areas By Phenotype

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

Mammalian Phenotype Terms by Genotype

Genotype: Il4ratm1Tch/Il4ratm1Tchinvolves: 129X1/SvJ * BALB/c

cellular phenotype

respiratory system phenotype

hematopoietic system phenotype

immune system phenotype

References

Additional - Il4ratm1Tch 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

Payment Terms and Conditions

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

Il4ra^tm1Tch

Allele Symbol: Il4ra^tm1Tch

Genotype: Il4ra^tm1Tch/Il4ra^tm1Tch
involves: 129X1/SvJ * BALB/c

Additional - Il4ra^tm1Tch related