Strain Name:

C.129X1-Il4ratm3.1Tch/J

Stock Number:

012709

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Cryopreserved - Ready for recovery

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Common Names: C.129.Il4ra<F709>;    
These Il4raF709 mutant mice harbor a Y709F polymorphism within the canonical immunoreceptor tyrosine-based inhibitory motif (ITIM) sequence near the carboxyl-terminus of the protein. This Y709F polymorphism prevents ITIM phosphorylation and disables the binding of regulatory phosphatases. These Il4raF709 mutant mice may be useful in immunological studies of mitogenic signal transduction, specifically antigen-specific antibody responses, allergic airway inflammation, atopy, asthma, and food allergy research.

Description

The genotypes of the animals provided may not reflect those discussed in the strain description or the mating scheme utilized by The Jackson Laboratory prior to cryopreservation. Please inquire for possible genotypes for this specific strain.

Strain Information

Former Names C.129X1-Il4ratm3Tch/J    (Changed: 17-JUN-10 )
Type Congenic; Mutant Strain; Targeted Mutation;
Additional information on Genetically Engineered and Mutant Mice.
Visit our online Nomenclature tutorial.
Additional information on Congenic nomenclature.
Specieslaboratory mouse
GenerationN12pN1
Generation Definitions
 
Donating Investigator Talal Chatila,   Boston Children's Hospital

Description
Mice homozygous for this Il4raF709 (IL-4Rα Y709F) polymorphic allele are viable and fertile. The mutation introduces a tyrosine to phenylalanine amino acid substitution at codon 709 (Y709F) within the canonical immunoreceptor tyrosine-based inhibitory motif (ITIM) sequence near the carboxyl-terminus of the protein. This Y709F polymorphism prevents ITIM phosphorylation and inhibit the binding of regulatory phosphatases (including Src homology 2 domain-containing protein tyrosine phosphatase 1 [SHP-1]), resulting in enhanced receptor signaling. Allele-specific PCR verifies the Y709 to F709 codon substitution. Homozygous mice exhibit enhanced phosphorylation of signal transducer and activator of transcription 6 (STAT6) in B cells following IL-4 treatment, and increased serum concentrations of total IgE and ovalbumin (OVA)-specific IgE after immunization with OVA/alum. Il4raF709/F709 mice have increased allergic airway inflammation (peribronchial and perivascular inflammation, goblet cells and eosinophil accumulation) and airway hyperresponsiveness in response to allergen sensitization and challenge. Both untreated and OVA-challenged homozygous mice exhibit upregulated expression of a number of STAT6-responsive genes involved in allergic airway inflammation. The Y709F substitution results in increased IL-4 production after Th2 polarization (Th2 bias) and enhanced alternative macrophage activiation by IL-13 in vivo. The Il4raF709/F709 mice are highly susceptible to oral sensitization to OVA, even in the absence of adjuvants, and sensitized mice respond to oral challenge with anaphylaxis. These Il4raF709 mutant mice may be useful in immunological studies of mitogenic signal transduction, specifically antigen-specific antibody responses, allergic airway inflammation, atopy, asthma, and food allergy research.

Development
Two base pair substitutions (A->T and C->T at basepair 2362 and 2363, respectively) were introduced into the murine Il4ra cDNA using site-directed mutagenesis. These mutations result in a single amino acid substitution of tyrosine to phenylalanine at codon 709 (Y709F) within the canonical immunoreceptor tyrosine-based inhibitory motif (ITIM) sequence near the carboxyl-terminus of the protein. A targeting vector that included these two mutations and a loxP-flanked neo cassette inserted into 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 neo selection cassette (leaving a single loxP site in intron 11) and then injected into recipient blastocysts. The resulting chimeric males were crossed to BALB/cAnNTac females. Heterozygotes were bred to BALB/cAnNTac for at least 10 generations prior to sending to The Jackson Laboratory Repository. Upon arrival, mice were bred to BALB/cByJ (Stock No. 001026) for at least one generation to establish the colony.

Control Information

  Control
   001026 BALB/cByJ (approximate)
 
  Considerations for Choosing Controls

Related Strains

Strains carrying other alleles of Il4ra
003514   BALB/c-Il4ratm1Sz/J
007680   C.129X1-Il4ratm1Tch/J
007746   C.129X1-Il4ratm2Tch/J
View Strains carrying other alleles of Il4ra     (3 strains)

Phenotype

Phenotype Information

View Related Disease (OMIM) Terms

Related Disease (OMIM) Terms provided by MGI
- Potential model based on gene homology relationships. Phenotypic similarity to the human disease has not been tested.
Human Immunodeficiency Virus Type 1, Susceptibility to   (IL4R)
IgE Responsiveness, Atopic; IGER   (IL4R)
View Mammalian Phenotype Terms

Mammalian Phenotype Terms provided by MGI
      assigned by genotype

Il4ratm3.1Tch/Il4ratm3.1Tch

        C.129X1-Il4ratm3.1Tch
  • immune system phenotype
  • abnormal macrophage activation involved in immune response
    • following exposure to IL4 and IL13, marker expression reveals enhanced alternative macrophage activation compared to in wild-type mice   (MGI Ref ID J:160806)
  • increased IgE level
    • following immunization with ovalbumin and alum adjuvant   (MGI Ref ID J:160806)
  • increased interleukin-4 secretion
  • increased susceptibility to type I hypersensitivity reaction
    • following airway ovalbumin sensitization, mice exhibit an increased accumulation of eosinophils in the bronchoalveolar lavage fluid compared with similarly treated wild-type mice   (MGI Ref ID J:160806)
  • hematopoietic system phenotype
  • abnormal macrophage activation involved in immune response
    • following exposure to IL4 and IL13, marker expression reveals enhanced alternative macrophage activation compared to in wild-type mice   (MGI Ref ID J:160806)
  • increased IgE level
    • following immunization with ovalbumin and alum adjuvant   (MGI Ref ID J:160806)
View Research Applications

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

Cell Biology Research
Signal Transduction

Hematological Research
Immunological Defects

Immunology, Inflammation and Autoimmunity Research
Autoimmunity
Growth Factors/Receptors/Cytokines
Immunodeficiency
      Asthma
      T cell deficiency
      multiple immune defects
Inflammation
      Asthma
Intracellular Signaling Molecules
Lymphoid Tissue Defects

Internal/Organ Research
Lymphoid Tissue Defects

Research Tools
Cell Biology Research
Hematological Research
Immunology, Inflammation and Autoimmunity Research
      T cell deficiency

Genes & Alleles

Gene & Allele Information provided by MGI

 
Allele Symbol Il4ratm3.1Tch
Allele Name targeted mutation 3.1, Talal A Chatila
Allele Type Targeted
Common Name(s) IL-4Ra Y709F; Il4raF709;
Mutation Made By Talal Chatila,   Boston Children's Hospital
Strain of Origin129X1/SvJ
Gene Symbol and Name Il4ra, interleukin 4 receptor, alpha
Chromosome 7
Gene Common Name(s) CD124; IL-4 receptor alpha chain; IL-4RA; Il4r; interleukin 4 receptor;
Molecular Note Two base pair substitutions (A->T and C->T at basepair 2362 and 2363, respectively) were introduced into the murine Il4ra cDNA using site-directed mutagenesis. These mutations result in a single amino acid substitution of tyrosine to phenylalanine at codon 709 (Y709F) within the canonical immunoreceptor tyrosine-based inhibitory motif (ITIM) sequence near the carboxyl-terminus of the protein. The targeting vector included these two mutations and a loxP-flanked neo cassette inserted into intron 11. Cre mdiated recombination removed the neo cassette. [MGI Ref ID J:160806]

Genotyping

Genotyping Information

Genotyping Protocols

Il4ratm3.1Tch, Standard PCR


Helpful Links

Genotyping resources and troubleshooting

References

References provided by MGI

Selected Reference(s)

Mathias CB; Hobson SA; Garcia-Lloret M; Lawson G; Poddighe D; Freyschmidt EJ; Xing W; Gurish MF; Chatila TA; Oettgen HC. 2011. IgE-mediated systemic anaphylaxis and impaired tolerance to food antigens in mice with enhanced IL-4 receptor signaling. J Allergy Clin Immunol 127(3):795-805.e1-6. [PubMed: 21167580]  [MGI Ref ID J:171808]

Tachdjian R; Al Khatib S; Schwinglshackl A; Kim HS; Chen A; Blasioli J; Mathias C; Kim HY; Umetsu DT; Oettgen HC; Chatila TA. 2010. In vivo regulation of the allergic response by the IL-4 receptor alpha chain immunoreceptor tyrosine-based inhibitory motif. J Allergy Clin Immunol 125(5):1128-1136.e8. [PubMed: 20392476]  [MGI Ref ID J:160806]

Health & husbandry

The genotypes of the animals provided may not reflect those discussed in the strain description or the mating scheme utilized by The Jackson Laboratory prior to cryopreservation. Please inquire for possible genotypes for this specific strain.

Health & Colony Maintenance Information

Animal Health Reports

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

Colony Maintenance

Breeding & HusbandryWhen maintaining a live colony, these mice may be bred as homozygotes.

Pricing and Purchasing

Pricing, Supply Level & Notes, Controls


Pricing for USA, Canada and Mexico shipping destinations View International Pricing

Cryopreserved

Cryopreserved Mice - Ready for Recovery

Price (US dollars $)
Cryorecovery* $3300.00
Animals Provided

At least two mice that carry the mutation (if it is a mutant strain) will be provided. Their genotypes may not reflect those discussed in the strain description. Please inquire for possible genotypes and see additional details below.

Standard Supply

Cryopreserved. Ready for recovery. Please refer to pricing and supply notes on the strain data sheet for further information.

Supply Notes

  • Cryorecovery - Standard.
    Progeny testing is not required.

    The average number of mice provided from recovery of our cryopreserved strains is 10. The total number of animals provided, their gender and genotype will vary. We will fulfill your order by providing at least two pair of mice, at least one animal of each pair carrying the mutation of interest. Please inquire if larger numbers of animals with specific genotype and genders are needed. Animals typically ship between 10 and 14 weeks from the date of your order. If a second cryorecovery is needed in order to provide the minimum number of animals, animals will ship within 25 weeks. IMPORTANT NOTE: The genotypes of animals provided may not reflect the mating scheme utilized by The Jackson Laboratory prior to cryopreservation, or that discussed in the strain description. Please inquire about possible genotypes which will be recovered for this specific strain. The Jackson Laboratory 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. For more information on Dedicated Supply, please contact JAX® Services, Tel: 1-800-422-6423 (from U.S.A., Canada or Puerto Rico only) or 1-207-288-5845 (from any location).

Pricing for International shipping destinations View USA Canada and Mexico Pricing

Cryopreserved

Cryopreserved Mice - Ready for Recovery

Price (US dollars $)
Cryorecovery* $4290.00
Animals Provided

At least two mice that carry the mutation (if it is a mutant strain) will be provided. Their genotypes may not reflect those discussed in the strain description. Please inquire for possible genotypes and see additional details below.

Standard Supply

Cryopreserved. Ready for recovery. Please refer to pricing and supply notes on the strain data sheet for further information.

Supply Notes

  • Cryorecovery - Standard.
    Progeny testing is not required.

    The average number of mice provided from recovery of our cryopreserved strains is 10. The total number of animals provided, their gender and genotype will vary. We will fulfill your order by providing at least two pair of mice, at least one animal of each pair carrying the mutation of interest. Please inquire if larger numbers of animals with specific genotype and genders are needed. Animals typically ship between 10 and 14 weeks from the date of your order. If a second cryorecovery is needed in order to provide the minimum number of animals, animals will ship within 25 weeks. IMPORTANT NOTE: The genotypes of animals provided may not reflect the mating scheme utilized by The Jackson Laboratory prior to cryopreservation, or that discussed in the strain description. Please inquire about possible genotypes which will be recovered for this specific strain. The Jackson Laboratory 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. For more information on Dedicated Supply, please contact JAX® Services, Tel: 1-800-422-6423 (from U.S.A., Canada or Puerto Rico only) or 1-207-288-5845 (from any location).

View USA Canada and Mexico Pricing View International Pricing

Standard Supply

Cryopreserved. Ready for recovery. Please refer to pricing and supply notes on the strain data sheet for further information.

Control Information

  Control
   001026 BALB/cByJ (approximate)
 
  Considerations for Choosing Controls
  Control Pricing Information for Genetically Engineered Mutant Strains.
 

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