These mice carry a W131A mutation that disrupts the autoinhibitory mechanism regulating Zap70 gene function. This model is useful for studying CD4 T cell anergy.
Dr. Arthur Weiss, University of California, San Francisco
Zap70 (zeta-chain (TCR) associated protein kinase) plays a critical role in normal T cell development and T cell function. Regulation of gene activity involves an allosteric autoinhibitory mechanism.
These targeted mutant animals carry a W131A mutation within the mouse Zap70 gene. This destabilizes the autoinhibitory conformation, placing the kinase in a semiactive state. Expression levels of ZAP70 protein are reduced by half in thymocytes and peripheral T cells of homozygotes.
W131A mice have a slight increase in T regulatory cells, but overall T cell development, T cell function, and T cell signaling appear normal. When W131A mice are crossed to OTII TCR transgenic mice (see Stock No. 004194), the W131A mutation leads to thymocyte negative selection and results in impaired peripheral T cell signaling and responses. This model is useful for studying CD4 T cell anergy.
A W131A (TGG->GCG) mutation was introduced to exon 2 and a neomycin cassette (flanked by loxP sites and inserted in reverse transcriptional orientation) was placed in intron 3 via homologous recombination in PRX-B6T C57BL/6-derived embryonic stem cells. The neomycin cassette was excised through crosses with mice expressing CMV-cre. Resultant mice were bred to inbred C57BL/6J mice for three generations by the donating laboratory.
|Allele Name||targeted mutation 3.1, Arthur Weiss|
|Allele Type||Targeted (Hypomorph)|
|Allele Synonym(s)||Zap70 W131A|
|Gene Symbol and Name||Zap70, zeta-chain (TCR) associated protein kinase|
|Gene Synonym(s)||ADMIO2; AI327364; IMD48; SRK; STCD; STD; Srk; Srk; TZK; ZAP-70; expressed sequence AI327364; mr t-less; mrtle; mur; murdoch; syk related kinase|
|Strain of Origin||C57BL/6J|
|Molecular Note||A W131A (TGG->GCG, tryptophan to alanine) mutation was introduced into exon 2 and a neomycin cassette (flanked by loxP sites and inserted in reverse transcriptional orientation) was placed in intron 3. Cre-mediated recombination removed the floxed neo cassette. The mutation, located in interdomain A reduces protein expression by 50% in thymocytes and peripheral T cells.|
Heterozygotes and homozygotes are viable and fertile. When maintaining a live colony, these mice can be bred as homozygotes.
When using the W131A mouse strain in a publication, please cite the originating article(s) and include JAX stock #030677 in your Materials and Methods section.
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