Description

Strain Information

Type Congenic; Mutant Strain; Targeted Mutation; Additional information on Genetically Engineered Mutant Mice. Mating System Homozygote x Homozygote         (Female x Male) Species laboratory mouse Generation N12F?+F4 (22-OCT-08)   Donating Investigator Talal Chatila,   David Geffen School of Medicine, UCLA

Description
Mice homozygous for this "IL4Ra Y500F" mutant allele are viable and fertile. The mice express a mutant IL4Ra 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 IL4Ra 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-4Ra 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 Information

	Control
	001026 BALB/cByJ	(approximate)
	000651 BALB/cJ	(approximate)
Considerations for Choosing Controls

Related Strains

Strains carrying other alleles of Il4ra

003514

BALB/c-Il4ratm1Sz/J

View Strains carrying other alleles of Il4ra     (1 strain)

Additional Web Information

Congenic Nomenclature

Phenotype

Phenotype Information

View Related Disease (OMIM) Terms

Related Disease (OMIM) Terms

Asthma, Susceptibility to - Models with phenotypic similarity to human disease where etiologies are distinct.2

2 Human genes are associated with this disease. Orthologs of those genes do not appear in the mouse genotype(s).

View Mammalian Phenotype Terms

Mammalian Phenotype Terms

      assigned by genotype

The following phenotype information may relate to a genetic background differing from this JAX^® Mice strain.

Il4ra^tm1Tch/Il4ra^tm1Tch

        involves: 129X1/SvJ * BALB/c

• immune system phenotype
• abnormal T-helper 2 cell morphology (MGI Ref ID J:86215)
  • decreased persistence of Th2 cells as indicated by Il-4, Il-5, and Il-13 production
  • Th2 differentiation not impaired however
• abnormal immune serum protein physiology (MGI Ref ID J:86215)
• increased IgE level (MGI Ref ID J:86215)
  • levels are substantially higher than normal
• increased IgG level (MGI Ref ID J:86215)
  • IgG1 and IgG2 levels are higher than normal in response to OVA stimulation
• decreased T cell proliferation (MGI Ref ID J:86215)
  • impaired Il-4 induced CD4⁺ T cell proliferation
• respiratory system inflammation (MGI Ref ID J:86215)
  • airway hyperresponsiveness to methacholine
  • eosinophilic infiltration
  • goblet cell hyperplasia
• respiratory system phenotype
• increased airway responsiveness (MGI Ref ID J:86215)
  • with methacholine challenge
• respiratory system inflammation (MGI Ref ID J:86215)
  • airway hyperresponsiveness to methacholine
  • eosinophilic infiltration
  • goblet cell hyperplasia
• hematopoietic system phenotype
• abnormal T-helper 2 cell morphology (MGI Ref ID J:86215)
  • 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 (MGI Ref ID J:86215)
  • impaired Il-4 induced CD4⁺ T cell proliferation

View Research Applications

Research Applications

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

Cell Biology Research
Signal Transduction

Diabetes and Obesity Research
Insulin Receptors and Growth Factors

Hematological Research
Immunological Defects

Immunology and Inflammation Research
Autoimmunity
Growth Factors/Receptors/Cytokines
Immunodeficiency (Asthma)
Immunodeficiency (T cell deficiency)
Immunodeficiency (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 and Inflammation Research (T cell deficiency)

Genes & Alleles

Gene & Allele Information

Allele Symbol		Il4ratm1Tch
Allele Name		targeted mutation 1, Talal A Chatila
Allele Type		Targeted (knock-in)
Common Name(s)		Y500F;
Mutation Made By		Talal Chatila,   David Geffen School of Medicine, UCLA
Strain of Origin		129X1/SvJ
ES Cell Line Name		RW-4
ES Cell Line Strain		129X1/SvJ
Gene Symbol and Name		Il4ra, interleukin 4 receptor, alpha
Chromosome		7
Gene Common Name(s)		CD124; IL-4 receptor alpha chain; Il4r; interleukin 4 receptor;
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 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. [MGI Ref ID J:86215]

Genotyping

Genotyping Information

Genotyping Protocols

Il4ra^tm1Tch, PYRO, vers. 1

Helpful Links

Optimizing PCR Protocols

References

References

Selected Reference(s)

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):1189-200. [PubMed: 14557412]  [MGI Ref ID J:86215]

Health & husbandry

Health & Colony Maintenance Information

Animal Health Reports

Room Number           AX11

Colony Maintenance

Breeding & Husbandry	When maintaining a live colony, these mice may be bred as homozygotes.
Mating System	Homozygote x Homozygote         (Female x Male)
Diet Information	LabDiet® 5K52/5K67

Purchasing information

Pricing, Supply Level & Notes, Controls, General Terms & Conditions

Pricing

Supply Details

Standard Supply

Repository-Live. A collection of over 1000 strains maintained as live colonies. Individual colonies are sized to meet current customer demand. Delivery for orders of 10 mice or less ranges on average from one to eight weeks; mice are generally shipped between four to six weeks of age with a maximum shipping age of ~nine weeks. Colony sizes do not generally support stringent age specifications for large volumes of mice; however custom orders and larger quantities of mice are easily arranged. Estimated ship dates for all orders provided within 48 hours of order placement.

Supply Notes

Usually shipped between four and eight weeks of age. This strain is included in the Induced Mutant Resource Colony collection.

Control Information

	Control
	001026 BALB/cByJ	(approximate)
	000651 BALB/cJ	(approximate)
Considerations for Choosing Controls
USA, Canada and Mexico - Control Pricing Information for Genetically Engineered Mutant Strains.
International - Control Pricing Information for Genetically Engineered Mutant Strains.

General Terms and Conditions

See Terms of Use

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.

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Ordering and Purchasing Information

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Contact Information
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Tel: 800.422.6423 or 207.288.5845
Fax: 207.288.6150
Technical Support Email Form

Terms of Use

Terms of Use

General Terms and Conditions

Effective September 26, 2007: License Requirements for Strains using Cre-lox Technology only apply in Canada, see Licenses for Strains using Cre-lox Technology.

Contact information

General inquiries

Contracts Administration

phone:	207-288-6470
fax:	207-288-6655

JAX^® Mice & Services Conditions of Use

“Each recipient institution, including its employees and other researchers under its control (RECIPIENT), of mice or services using mice from The Jackson Laboratory (TJL) agrees that such mice, descendants of those mice derived by inbreeding or crossbreeding, including unmodified derivatives of those mice or their descendants (“MICE”) shall not be: (i) used for any purpose other than the internal research of the RECIPIENT, (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 with respect to MICE. Acceptance of MICE from TJL shall be deemed agreement by RECIPIENT to these conditions, and departure from these conditions requires The Jackson Laboratory’s prior written authorization.”

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