Table 1.
Association of Janus kinases (Jaks), Signal transducers and activators of transcription (Stats), and suppressors of cytokine signaling (SOCSs) with cytokine receptors and phenotype of knockout mice.
| Jak/Stat/SOCS | Cytokines | Deficient mice |
| Jak1 | γccytokines, gp130 cytokines, IL-10, IFN-α , IFN-β , IFN-γ, IL-13 | Neurologic defect (?), mice die perinatally |
| Jak2 | Erythropoietin, βccytokines, gp130 cytokines, IL-13, IL-12, GH, prolactin, thrombopoietin, IFN-γ | Embryonically lethal, failed to develop red blood cells |
| Jak3 | IL-2, IL-7, IL-15, γc cytokines | SCID |
| Tyk2 | gp130 cytokines, IL-13, IL-12, IFN-α, IFN-β, IL-10 | Not yet reported |
| Stat1 | IFN-α , IFN-β , IFN-γ , IL-2, IL-6, IL-10 | Susceptibility to viral and some bacterial infections |
| Defective signaling in response to IFNs | ||
| Impaired tumor rejection | ||
| Stat2 | IFN-α, IFN-β | Defective signaling in response to IFNs* |
| Stat3 | LIF, IL-10, IL-6, other gp130 cytokines, γc cytokines, GH | Embryonically lethal |
| Targeted disruption in macrophages and neutrophils showed defective | ||
| IL-6 and IL-10 signaling | ||
| Chronic enterocolitis | ||
| Conditional knockouts showed suppressed epithelial apoptosis and | ||
| delayed mammary gland involution | ||
| Stat4 | IL-12 | Defective Th1 development |
| Stat5a | Prolactin, other γc cytokines, otherβc cytokines, GH, thrombopoietin | Defective lobuloalveolar development in breast |
| Stat5b | GH, other γc cytokines,βc cytokines, prolactin, thrombopoietin | Required for sexual dimorphism |
| Stat5a/b | GH, IL-2, erythropoietin | Infertile, smaller body size |
| Impaired cell-cycle progression of peripheral T cells | ||
| Fetal anemia (?) | ||
| Stat6 | IL-4, IL-13 | Defective Th2 development |
| Stat4/6 | No Th2 cells in vitro | |
| SOCS-1 | IFN-γ, IL-6, GH, thrombopoietin, OSM, LIF | Perinatal lethality, hyper-responsiveness to IFN-γ |
| SOCS-3 | Erythropoietin, GH, IL-2, leptin, CNTF, IL-11, IL-10 | Embryonic lethality, ? due to erythrocytosis |
γ Chain (γc) cytokines: interleukin (IL)- 2, IL- 4, IL- 7, IL- 9, IL- 15. gp130 cytokines: IL- 6, IL- 11, oncostatin M (OSM), ciliary neurotropic factor (CNTF), leukemia inhibitory factor (LIF), CT- 1, IL- 12, Leptin. β chain (βc) cytokines: IL- 3, IL- 5, granulocyte- macrophage colony- stimulating factor (GM- CSF). Bold letters indicate cytokines that have been shown to be essential in knockouts. *Schindler C, personal communication. SCID, severe combined immunodeficiency; FGF, fibroblast gowth factor; GH, growth factor; IFN, interferon.