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
Genetic Background | Generation |
---|---|
|
Allele Type | Gene Symbol | Gene Name |
---|---|---|
Targeted (Null/Knockout) | Foxp3 | forkhead box P3 |
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) | Foxp3-; Foxp3K276X |
Gene Symbol and Name | Foxp3, forkhead box P3 |
Gene Synonym(s) | |
Strain of Origin | 129X1/SvJ |
Chromosome | X |
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.
Facility Barrier Level Descriptions
Service/Product | Description | Price |
---|---|---|
X Linked -Heterozygous females and Non carrier males |
Frozen Mouse Embryo | C.Cg-Foxp3<tm1Tch>/J | $2595.00 |
Frozen Mouse Embryo | C.Cg-Foxp3<tm1Tch>/J | $2595.00 |
Frozen Mouse Embryo | C.Cg-Foxp3<tm1Tch>/J | $3373.50 |
Frozen Mouse Embryo | C.Cg-Foxp3<tm1Tch>/J | $3373.50 |
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