|Coordinate||36,781,149 bp (GRCm38)|
|Base Change||T ⇒ C (forward strand)|
|Gene Name||zeta-chain (TCR) associated protein kinase|
|Synonym(s)||ZAP-70, TZK, Srk|
|Chromosomal Location||36,761,798-36,782,818 bp (+)|
FUNCTION: This gene encodes a member of the protein tyrosine kinase family. The encoded protein is essential for development of T lymphocytes and thymocytes, and functions in the initial step of T lymphocyte receptor-mediated signal transduction. A mutation in this gene causes chronic autoimmune arthritis, similar to rheumatoid arthritis in humans. Mice lacking this gene are deficient in alpha-beta T lymphocytes in the thymus. In humans, mutations in this gene cause selective T-cell defect, a severe combined immunodeficiency disease characterized by a selective absence of CD8-positive T lymphocytes. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jan 2014]
PHENOTYPE: Mutant mice show T cell defects. Null mutants lack alpha-beta T cells in the thymus and have fewer T cells in dendritic and intestinal epithelium. Spontaneous and knock-in missense mutations affect T cell receptor signaling, one of the former resulting in severe chronic arthritis. [provided by MGI curators]
|Amino Acid Change||Tryptophan changed to Arginine|
|Institutional Source||Australian Phenomics Network|
W504R in Ensembl: ENSMUSP00000027291 (fasta)
|Gene Model||not available|
|Predicted Effect||probably damaging
PolyPhen 2 Score 1.000 (Sensitivity: 0.00; Specificity: 1.00)
|Alleles Listed at MGI|
|Mode of Inheritance||Autosomal Recessive|
Australian PhenomeBank: 158
|Last Updated||2017-08-08 8:07 PM by Diantha La Vine|
|Record Created||2010-05-26 9:30 AM by Nora G. Smart|
The mrtless (mrt) phenotype was identified in a flow cytometry screen of blood from N-ethyl-N-nitrosourea (ENU)-mutagenized mice for mutations affecting the circulating proportions of memory and naïve T cells (1). Homozygous mrtless mice display an almost complete arrest of T cell development at the CD4+CD8+ double positive (DP) stage resulting in very few peripheral T cells. Cluster of differentiation 5 (CD5) and CD69 are upregulated on T cells in response to T cell activation. A comparison of CD5 and CD69 expression in Zap70mrt/mrt and homozygous null Zap70−/− animals established that Zap70mrt/mrt thymocytes have greater responsiveness to TCR stimulation than thymocytes with no ZAP-70 (Figure 1).
Please see the record for murdock for more information about the Zap70mrt allele.
|Nature of Mutation|
The mrtless mutation was mapped to Chromosome 1, and corresponds to a T to C transition at position 1601 of the Zap70 transcript, in exon 11 of 13 total exons.
The mutated nucleotide is indicated in red lettering and causes a tryptophan to arginine change at amino acid 504 of the encoded protein.
Please see the record for murdock for more information about Zap70.
|Primers||Primers cannot be located by automatic search.|
Genotyping protocols are from the Australian PhenomeBank.
1. Siggs, O. M., Miosge, L. A., Yates, A. L., Kucharska, E. M., Sheahan, D., Brdicka, T., Weiss, A., Liston, A., and Goodnow, C. C. (2007) Opposing Functions of the T Cell Receptor Kinase ZAP-70 in Immunity and Tolerance Differentially Titrate in Response to Nucleotide Substitutions. Immunity. 27, 912-926.
|Science Writers||Nora G. Smart|
|Illustrators||Diantha La Vine|
|Authors||Owen M. Siggs, Lisa A. Miosge, Adele L. Yates, Edyta M. Kucharska, Daniel Sheahan, Tomas Brdicka, Arthur Weiss, Adrian Liston, and Christopher C. Goodnow.|