Overview

These Il4ra^R576 mutant mice (harboring the Q576R polymorphism) may be useful in immunological studies of mitogenic signal transduction, specifically antigen-specific antibody responses, allergic airway inflammation, atopy, and asthma.

Donating Investigator

Talal Chatila, Boston Children's Hospital

Genetic overview

Genetic Background	Generation

Il4ra^tm2Tch

Allele Type	Gene Symbol	Gene Name
Targeted	Il4ra	interleukin 4 receptor, alpha

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Research Applications

Immunology, Inflammation and Autoimmunity Research
Internal/Organ Research
Research Tools
Cell Biology Research
Hematological 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 Q576R polymorphic allele (Il4ra^R576) are viable and fertile. The mutation introduces an arginine substitution at glutamine 576 (Q576R) in the protein sequence. This polymorphism is associated with severe asthma susceptibility and rapid smoking-associated lung function decline in human populations. Allele-specific PCR verifies the amino acid substitution. Homozygous mice exhibit heightened IgE responses in vivo, and augmented antigen- and IL-13-driven allergic airway inflammation. T cells from homozygotes show increased production of IL-4 in a Th2 polarized milieu. The R576 substitution is associated with enhanced Erk kinase activation with no reported effect on the activation of other canonical IL-4Rα-coupled pathways. These Il4ra^R576 mutant mice may be useful in immunological studies of mitogenic signal transduction, specifically antigen-specific antibody responses, allergic airway inflammation, atopy, and asthma.

Development

Two base pair substitutions, (adenine (A) to guanine (G) and G to A at basepair 1964 and 1965, respectively), were introduced into the Il4ar gene using site-directed mutagenesis. These mutations result in a single amino acid substitution of glutamine to arginine at codon 576 (Q576R). A targeting vector which included these two mutations and a loxp-flanked PGK-neo cassette inserted within intron 11. 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 PGK-neo 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/cAnNTac females. Heterozygotes were bred to BALB/cAnNTac for at least 10 generations prior to the strain's arrival at The Jackson Laboratory.

Control Suggestions

Approximate Controls

Additional Information

Considerations for Choosing Controls

Selected References

Tachdjian R; Mathias C; Al Khatib S; Bryce PJ; Kim HS; Blaeser F; O'Connor BD; Rzymkiewicz D; Chen A; Holtzman MJ; Hershey GK; Garn H; Harb H; Renz H; Oettgen HC; Chatila TA. 2009. Pathogenicity of a disease-associated human IL-4 receptor allele in experimental asthma. J Exp Med 206(10):2191-204PubMed: 19770271 MGI: J:152376

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Genetics

Il4ra^tm2Tch

Allele Symbol: Il4ra^tm2Tch

Allele Name	targeted mutation 2, Talal A Chatila
Allele Type	Targeted
Allele Synonym(s)	Il4ra^R576; IL-4RalphaR576; Q576R
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	The targeting vector was designed (by site-directed mutagenesis) to change the alanine-guanine to guanine-alanine at basepair 1964-65 of murine IL-4Ra cDNA, corresponding to a single amino acid substitution of glutamine to arginine at codon 576 (Q576R). This also inserted a loxp-flanked PGK-neo cassette 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.
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
- Autoimmunity
- Intracellular Signaling Molecules
- Lymphoid Tissue Defects
- Growth Factors/Receptors/Cytokines
Internal/Organ Research
- Lymphoid Tissue Defects
Research Tools
- Immunology, Inflammation and Autoimmunity Research
  - T cell deficiency
- Cell Biology Research
- Hematological Research
Cell Biology Research
- Signal Transduction
Hematological Research
- Immunological Defects

Mammalian Phenotype Terms by Genotype

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

Genotype: Il4ra^tm2Tch/Il4ra^tm2Tch
C.129X1-Il4ra

respiratory system phenotype

increased respiratory mucosa goblet cell number
- OVA or IL13 challenged mice exhibit goblet cell hyperplasia

abnormal bronchus morphology
- OVA sensitized and challenged mutant (R576) mice exhibit patchy peribronchial inflammatory infiltrate that is more prominent that in Q576 controls
- peribronchial infiltrate is composed primarily of eosinophils and lymphoctyes

increased airway responsiveness
- enhanced response to IL13 challenge

respiratory system inflammation
- mutant mice exhibit airway inflammation following chronic allergen challenge
- increase in peribronchial and perivascular inflammation compared with control

hematopoietic system phenotype

increased eosinophil cell number
- increase in eosinophils found in lung parenchyma of OVA sensitized mutant mice

abnormal T-helper 2 physiology
- stimulated Th2 cells exhibit an increase in IL4 production, but not IL5 or IL13

increased IgE level
- following immunization with OVA or alum

increased monocyte cell number
- increase in monocytes found in lung parenchyma of OVA sensitized mutant mice

homeostasis/metabolism phenotype

increased circulating interleukin-4 level
- stimulated Th2 cells exhibit an increase in IL4 production

immune system phenotype

increased circulating interleukin-4 level
- stimulated Th2 cells exhibit an increase in IL4 production

increased eosinophil cell number
- increase in eosinophils found in lung parenchyma of OVA sensitized mutant mice

increased IgE level
- following immunization with OVA or alum

increased monocyte cell number
- increase in monocytes found in lung parenchyma of OVA sensitized mutant mice

respiratory system inflammation
- mutant mice exhibit airway inflammation following chronic allergen challenge
- increase in peribronchial and perivascular inflammation compared with control

abnormal T-helper 2 physiology
- stimulated Th2 cells exhibit an increase in IL4 production, but not IL5 or IL13

increased susceptibility to type I hypersensitivity reaction
- enhanced allergic inflammatory response following IL13 challenge

References

Tachdjian R; Mathias C; Al Khatib S; Bryce PJ; Kim HS; Blaeser F; O'Connor BD; Rzymkiewicz D; Chen A; Holtzman MJ; Hershey GK; Garn H; Harb H; Renz H; Oettgen HC; Chatila TA. 2009. Pathogenicity of a disease-associated human IL-4 receptor allele in experimental asthma. J Exp Med 206(10):2191-204PubMed: 19770271 MGI: J:152376

Additional - Il4ra^tm2Tch 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^tm2Tch/J mouse strain in a publication, please cite the originating article(s) and include JAX stock #007746 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<tm2Tch>

Related Products and Services

Frozen Mouse Embryo	C.129X1-Il4ra<tm2Tch>/J	$2595.00
Frozen Mouse Embryo	C.129X1-Il4ra<tm2Tch>/J	$2595.00
Frozen Mouse Embryo	C.129X1-Il4ra<tm2Tch>/J	$3373.50
Frozen Mouse Embryo	C.129X1-Il4ra<tm2Tch>/J	$3373.50

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

Terms Of Use

General Terms and Conditions

Questions about Terms of Use

Additional Use Restrictions Apply

Use of MICE by companies or for-profit entities requires a license prior to shipping.

Licensing Information

Phone: 207-288-6470

Email: TechTran@jax.org

Donating Investigator

Genetic overview

Research Applications

Base Price

Detailed Description

Development

Control Suggestions

Approximate Controls

Additional Information

Selected References

Il4ratm2Tch

Allele Symbol: Il4ratm2Tch

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: Il4ratm2Tch/Il4ratm2TchC.129X1-Il4ra

respiratory system phenotype

hematopoietic system phenotype

homeostasis/metabolism phenotype

immune system phenotype

References

Additional - Il4ratm2Tch 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

Il4ra^tm2Tch

Allele Symbol: Il4ra^tm2Tch

Genotype: Il4ra^tm2Tch/Il4ra^tm2Tch
C.129X1-Il4ra

Additional - Il4ra^tm2Tch related