SOCS1 deficiency causes a lymphocyte-dependent perinatal lethality.
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.
Marine
J C
JC
Howard Hughes Medical Institute, and Department of Biochemistry, St. Jude Children's Research Hospital, Memphis, Tennessee 38105, USA.
Topham
D J
DJ
McKay
C
C
Wang
D
D
Parganas
E
E
Stravopodis
D
D
Yoshimura
A
A
Ihle
J N
JN
D000367:Age Factors; D000818:Animals; D000831:Animals, Newborn; D002352:Carrier Proteins / Q000235:genetics* / Q000502:physiology*; D004268:DNA-Binding Proteins; D004305:Dose-Response Relationship, Drug; D005434:Flow Cytometry; D018507:Gene Expression Regulation, Developmental; D007371:Interferon-gamma / Q000494:pharmacology; D053616:Janus Kinase 3; D008214:Lymphocytes / Q000502:physiology*; D051379:Mice; D008817:Mice, Mutant Strains; D011505:Protein-Tyrosine Kinases / Q000502:physiology; D012097:Repressor Proteins; D000071222:Suppressor of Cytokine Signaling 1 Protein; D050826:Suppressor of Cytokine Signaling Proteins; D013601:T-Lymphocytes / Q000378:metabolism; D013950:Thymus Gland / Q000196:embryology / Q000378:metabolism; D014018:Tissue Distribution
D002352:Carrier Proteins; D004268:DNA-Binding Proteins; C499308:Rag2 protein, mouse; D012097:Repressor Proteins; C491590:Socs1 protein, mouse; D000071222:Suppressor of Cytokine Signaling 1 Protein; D050826:Suppressor of Cytokine Signaling Proteins; C064655:V(D)J recombination activating protein 2; D007371:Interferon-gamma; D011505:Protein-Tyrosine Kinases; C507935:Jak3 protein, mouse; D053616:Janus Kinase 3