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PMID:9826711
| Citation |
Starr, R, Metcalf, D, Elefanty, AG, Brysha, M, Willson, TA, Nicola, NA, Hilton, DJ and Alexander, WS (1998) Liver degeneration and lymphoid deficiencies in mice lacking suppressor of cytokine signaling-1. Proc. Natl. Acad. Sci. U.S.A. 95:14395-9 |
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| Abstract |
SOCS-1, a member of the suppressor of cytokine signaling (SOCS) family, was identified in a genetic screen for inhibitors of interleukin 6 signal transduction. SOCS-1 transcription is induced by cytokines, and the protein binds and inhibits Janus kinases and reduces cytokine-stimulated tyrosine phosphorylation of signal transducers and activators of transcription 3 and the gp130 component of the interleukin 6 receptor. Thus, SOCS-1 forms part of a feedback loop that modulates signal transduction from cytokine receptors. To examine the role of SOCS-1 in vivo, we have used gene targeting to generate mice lacking this protein. SOCS-1(-/-) mice exhibited stunted growth and died before weaning with fatty degeneration of the liver and monocytic infiltration of several organs. In addition, the thymus of SOCS-1(-/-) mice was reduced markedly in size, and there was a progressive loss of maturing B lymphocytes in the bone marrow, spleen, and peripheral blood. Thus, SOCS-1 is required for in vivo regulation of multiple cell types and is indispensable for normal postnatal growth and survival. |
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| Keywords |
Abnormalities, Multiple/genetics; Abnormalities, Multiple/pathology; Aging; Animals; Bone Marrow Cells/cytology; Bone Marrow Cells/immunology; Bone Marrow Cells/physiology; Carrier Proteins/genetics; Carrier Proteins/physiology; Enzyme Inhibitors; Hematocrit; Interleukin-6/physiology; Leukocyte Count; Liver/abnormalities; Liver/pathology; Lymphocytes/cytology; Lymphocytes/immunology; Lymphoid Tissue/abnormalities; Lymphoid Tissue/pathology; Mice; Mice, Knockout; Phenotype; Platelet Count; Protein-Tyrosine Kinases/antagonists & inhibitors; Recombination, Genetic; Repressor Proteins; Restriction Mapping; Signal Transduction; Spleen/immunology; Stem Cells; Suppressor of Cytokine Signaling Proteins; Thymus Gland/immunology |
| edit table |
Significance
Annotations
| Gene product | Qualifier | GO Term | Evidence Code | with/from | Aspect | Extension | Notes | Status |
|---|---|---|---|---|---|---|---|---|
| GO:0048589: developmental growth |
ECO:0000315: |
P |
Fig. 2 |
complete | ||||
See also
References
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