Liver degeneration and lymphoid deficiencies in mice lacking suppressor of cytokine signaling-1.
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.
Starr
R
R
Walter and Eliza Hall Institute of Medical Research and Cooperative Research Centre for Cellular Growth Factors, Post Office Royal Melbourne Hospital, Victoria 3050, Australia.
Metcalf
D
D
Elefanty
A G
AG
Brysha
M
M
Willson
T A
TA
Nicola
N A
NA
Hilton
D J
DJ
Alexander
W S
WS
D000015:Abnormalities, Multiple / Q000235:genetics / Q000473:pathology; D000375:Aging; D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology / Q000276:immunology / Q000502:physiology; D002352:Carrier Proteins / Q000235:genetics / Q000502:physiology*; D004791:Enzyme Inhibitors; D006400:Hematocrit; D015850:Interleukin-6 / Q000502:physiology*; D007958:Leukocyte Count; D008099:Liver / Q000002:abnormalities / Q000473:pathology*; D008214:Lymphocytes / Q000166:cytology / Q000276:immunology; D008221:Lymphoid Tissue / Q000002:abnormalities / Q000473:pathology*; D051379:Mice; D018345:Mice, Knockout; D010641:Phenotype; D010976:Platelet Count; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors; D011995:Recombination, Genetic; D012097:Repressor Proteins; D015183:Restriction Mapping; D015398:Signal Transduction; D013154:Spleen / Q000276:immunology; D013234:Stem Cells; D000071222:Suppressor of Cytokine Signaling 1 Protein; D050826:Suppressor of Cytokine Signaling Proteins; D013950:Thymus Gland / Q000276:immunology
D002352:Carrier Proteins; D004791:Enzyme Inhibitors; D015850:Interleukin-6; D012097:Repressor Proteins; C491590:Socs1 protein, mouse; D000071222:Suppressor of Cytokine Signaling 1 Protein; D050826:Suppressor of Cytokine Signaling Proteins; D011505:Protein-Tyrosine Kinases