Defective Lymphoid Development in Mice Lacking Jak3

• Published in: Science (American Association for the Advancement of Science) Vol. 270; no. 5237; pp. 800 - 802
• Main Authors: Nosaka, Tetsuya, Jan M. A. van Deursen, Tripp, Ralph A., Thierfelder, William E., Witthuhn, Bruce A., McMickle, Anthony P., Doherty, Peter C., Grosveld, Gerard C., Ihle, James N.
• Format: Journal Article
• Language: English
• Published: Washington, DC American Society for the Advancement of Science 03.11.1995; American Association for the Advancement of Science; The American Association for the Advancement of Science
• Subjects: Aging - immunology; Animals; Antigens, CD - metabolism; B lymphocytes; B-Lymphocytes - immunology; Biological and medical sciences; Chimera; Coding; DNA probes; Female; Fundamental and applied biological sciences. Psychology; Fundamental immunology; Gene Targeting; Genes; Genetically modified mice; Genetics of the immune response; Immunobiology; Individualized Instruction; Interleukin-7 - metabolism; Interleukin-7 - pharmacology; Janus Kinase 3; Lymphatic system; Lymphocyte Activation; Lymphocyte Count; Lymphocyte Subsets - immunology; Lymphoid tissue; Lymphoid Tissue - pathology; Male; Mice; Mice, Inbred C57BL; Numbers; Phenotype; Phenotypes; Protein tyrosine kinase; Protein-Tyrosine Kinases - genetics; Protein-Tyrosine Kinases - physiology; Receptors; Receptors, Interleukin - metabolism; Receptors, Interleukin-7; Rodents; Severe combined immunodeficiency; Signal Transduction; Spleen; Splenocytes; T lymphocytes; T-Lymphocytes - immunology; Thymocytes; Lymphoid cell; Enzyme; Transferases; Cytokine; Rodentia; Cell differentiation; Signal transduction; Vertebrata; Immunogenetics; Mammalia; Gene; Interleukin 2; Mouse; Mutation; Combined immune deficiency; Protein-tyrosine kinase; Biological receptor
• ISSN: 0036-8075; 1095-9203
• DOI: 10.1126/science.270.5237.800

The Janus tyrosine kinases (Jaks) play a central role in signaling through cytokine receptors. Although Jak1, Jak2, and Tyk2 are widely expressed, Jak3 is predominantly expressed in hematopoietic cells and is known to associate only with the common γ ($\gamma_c$) chain of the interleukin (IL)-2, IL-4, IL-7, IL-9, and IL-15 receptors. Homozygous mutant mice in which the Jak3 gene had been disrupted were generated by gene targeting. Jak3-deficient mice had profound reductions in thymocytes and severe B cell and T cell lymphopenia similar to severe combined immunodeficiency disease (SCID), and the residual T cells and B cells were functionally deficient. Thus, Jak3 plays a critical role in $\gamma_c$ signaling and lymphoid development.