These Foxp3K276X (forkhead box P3) mutant mice exhibit multisystem lymphoproliferative and myeloproliferative disease, and have applications in studies of T regulatory (Treg) cell function and allergic inflammation.
Talal Chatila, Boston Children's Hospital
The transcriptional regulator FOXP3 is in the forkhead/winged-helix family and is important in T regulatory cells (Tregs) development and function. These mice carry a targeted mutation of the Foxp3 gene that contains the K276X nonsense mutation (A to T substitution in the first base position of codon 276) in exon 8, which creates a stop codon. Female mice that are heterozygous for the mutation are viable and fertile. Male mice carrying this X-linked mutation die within a few weeks after birth, due to aggressive lymphoproliferative and myeloproliferative disease. No gene product (mRNA or protein) is detected by Real-time PCR or FACS analysis of mutant splenocytes. Null mice exhibit decreased numbers of B cells. By 2 weeks of age, mutant male mice exhibit spontaneous allergic airway inflammation, progressive lymphoproliferation and myeloproliferation and blood eosinophilia. Male hemizygotes on a congenic C57BL/6 background live longer (up to 60 days) than male hemizygotes on a BALB/c background (up to 23 days).
A targeting vector designed by Dr. Talal A. Chatila (UCLA) containing a loxP flanked NEO cassette was used to introduce the K276X nonsense mutation (A to T substitution in the first base position of codon 276) in exon 8, creating a stop codon. The construct was electroporated into 129X1/SvJ derived RW4 embryonic stem (ES) cells. Correctly targeted ES cells were injected into C57BL/6 blastocysts. The resulting chimeric male animals were crossed to BALB/c female mice. The mice were then crossed to EIIa-cre deleter mice on a mixed BALB/c, C57BL/6 background to remove the floxed NEO cassette. The mice were then backcrossed to BALB/c for 15 generations. Upon arrival at The Jackson Laboratory, the mice were crossed to BALB/cJ
(Stock No. 000651) at least once to establish the colony.
|Allele Name||targeted mutation 1, Talal A Chatila|
|Allele Type||Targeted (Null/Knockout)|
|Allele Synonym(s)||Foxp3tm1Tch; targeted mutation 1, Talal A Chatila|
|Gene Symbol and Name||Foxp3, forkhead box P3|
|Gene Synonym(s)||AIID; sf; DIETER; IPEX; PIDX; scurfin; XPID; JM2; scurfy; RGD1562112|
|Strain of Origin||129X1/SvJ|
|Molecular Note||A vector was designed to change codon K276 to a stop codon in exon 8. A neo included in the vector was subsequently removed via cre mediated recombination.|
When maintaining a live colony, female mice can be bred as heterozygotes. Male mice carrying this X-linked mutation die within a few weeks after birth, due to aggressive lymphoproliferative and myeloproliferative disease.
When using the Foxp3K276X BALB/c mouse strain in a publication, please cite the originating article(s) and include JAX stock #021144 in your Materials and Methods section.
|H Linked -Heterozygous females and Non carrier males|
We will fulfill your order by providing at least two carriers for each strain ordered. The total number, sex, and genotypes provided will vary, although typically 8 or more animals are provided. Please check genotypes which will be recovered. While the genotypes of all animals produced will be communicated to you prior to scheduling shipment, the genotypes of animals provided may not reflect the mating scheme and genotypes described in the strain description. Animals are typically ready to ship in 11-14 weeks. If a second recovery is required to produce the minimum number of animals, then delivery time would increase to approximately 25 weeks. If we fail to produce animals of the correct genotype, you will not be charged. We 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.
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