A novel Zap70 mutation with reduced protein stability demonstrates the rate‐limiting threshold for Zap70 in T‐cell receptor signalling

• Published in: Immunology Vol. 141; no. 3; pp. 377 - 387
• Main Authors: Cauwe, Bénédicte, Tian, Lei, Franckaert, Dean, Pierson, Wim, Staats, Kim A., Schlenner, Susan M., Liston, Adrian
• Format: Journal Article
• Language: English
• Published: England Wiley Subscription Services, Inc 01.03.2014; John Wiley & Sons Ltd
• Subjects: Amino Acid Sequence; Animals; Calcium Signaling; Cell Differentiation; Disease Models, Animal; Female; Forkhead Transcription Factors - metabolism; Foxp3; Genetic Predisposition to Disease; Heterozygote; Kinetics; Lymphocytes; Male; Mice; Mice, Inbred C57BL; Mice, Mutant Strains; Molecular Sequence Data; Mutation; N‐ethyl‐N‐nitrosourea mutagenesis; Original; Phenotype; Protein Stability; protein stabilization; Proteins; Receptors, Antigen, T-Cell - metabolism; Severe Combined Immunodeficiency - enzymology; Severe Combined Immunodeficiency - genetics; Severe Combined Immunodeficiency - immunology; Spleen - enzymology; Spleen - immunology; T cell; T cell receptors; T-Lymphocyte Subsets - enzymology; T-Lymphocyte Subsets - immunology; Thymocytes - enzymology; Thymocytes - immunology; T‐cell receptor; ZAP-70 Protein-Tyrosine Kinase - deficiency; ZAP-70 Protein-Tyrosine Kinase - genetics; ZAP-70 Protein-Tyrosine Kinase - immunology; ZAP-70 Protein-Tyrosine Kinase - metabolism; Zap70; T-cell receptor; Zap70; Foxp3; N-ethyl-N-nitrosourea mutagenesis; T cell; protein stabilization

Summary Loss of ζ‐associated protein 70 (Zap70) results in severe immunodeficiency in humans and mice because of the critical role of Zap70 in T‐cell receptor (TCR) signalling. Here we describe a novel mouse strain generated by N‐ethyl‐N‐nitrosourea mutagenesis, with the reduced protein stability (r...