These Il4raR576 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.
Talal Chatila, Boston Children's Hospital
Genetic Background | Generation |
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Allele Type | Gene Symbol | Gene Name |
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Targeted | Il4ra | interleukin 4 receptor, alpha |
Mice homozygous for this IL4Rα Q576R polymorphic allele (Il4raR576) 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 Il4raR576 mutant mice may be useful in immunological studies of mitogenic signal transduction, specifically antigen-specific antibody responses, allergic airway inflammation, atopy, and asthma.
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.
Allele Name | targeted mutation 2, Talal A Chatila |
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Allele Type | Targeted |
Allele Synonym(s) | Il4raR576; 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 |
When maintaining a live colony, these mice may be bred as homozygotes.
When using the C.129X1-Il4ratm2Tch/J mouse strain in a publication, please cite the originating article(s) and include JAX stock #007746 in your Materials and Methods section.
Facility Barrier Level Descriptions
Service/Product | Description | Price |
---|---|---|
Heterozygous for Il4ra<tm2Tch> |
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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