Abstract
SOCS1 is an SH2-containing protein that is primarily expressed in thymocytes in a cytokine- and T cell receptor-independent manner. SOCS1 deletion causes perinatal lethality with death by 2-3 weeks. During this period thymic changes include a loss of cellularity and a switch from predominantly CD4+ CD8+ to single positive cells. Peripheral T cells express activation antigens and proliferate to IL-2 in the absence of anti-CD3. In addition, IFNgamma is present in the serum. Reconstitution of the lymphoid lineage of JAK3-deficient mice with SOCS1-deficient stem cells recapitulates the lethality and T cell alterations. Introducing a RAG2 or IFNgamma deficiency eliminates lethality. The results demonstrate that lymphocytes are critical to SOCS1-associated perinatal lethality and implicate SOCS1 in lymphocyte differentiation or regulation.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Age Factors
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Animals
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Animals, Newborn
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Carrier Proteins / genetics*
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Carrier Proteins / physiology*
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DNA-Binding Proteins
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Dose-Response Relationship, Drug
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Flow Cytometry
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Gene Expression Regulation, Developmental*
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Interferon-gamma / pharmacology
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Janus Kinase 3
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Lymphocytes / physiology*
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Mice
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Mice, Mutant Strains
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Protein-Tyrosine Kinases / physiology
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Repressor Proteins*
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Suppressor of Cytokine Signaling 1 Protein
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Suppressor of Cytokine Signaling Proteins
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T-Lymphocytes / metabolism
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Thymus Gland / embryology
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Thymus Gland / metabolism
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Tissue Distribution
Substances
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Carrier Proteins
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DNA-Binding Proteins
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Rag2 protein, mouse
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Repressor Proteins
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Socs1 protein, mouse
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Suppressor of Cytokine Signaling 1 Protein
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Suppressor of Cytokine Signaling Proteins
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V(D)J recombination activating protein 2
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Interferon-gamma
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Protein-Tyrosine Kinases
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Jak3 protein, mouse
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Janus Kinase 3