SOCS1 deficiency causes a lymphocyte-dependent perinatal lethality

Jean Christophe Marine, David J. Topham, Catriona McKay, Demin Wang, Evan Parganas, Dimitrios Stravopodis, Akihiko Yoshimura, James N. Ihle

Research output: Contribution to journalArticle

423 Citations (Scopus)

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, IFNγ, 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 IFNγ, deficiency eliminates lethality. The results demonstrate that lymphocytes are critical to SOCS1-associated perinatal lethality and implicate SOCS1 in lymphocyte differentiation or regulation.

Original languageEnglish
Pages (from-to)609-616
Number of pages8
JournalCell
Volume98
Issue number5
DOIs
Publication statusPublished - 1999 Sep 3
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

Fingerprint Dive into the research topics of 'SOCS1 deficiency causes a lymphocyte-dependent perinatal lethality'. Together they form a unique fingerprint.

  • Cite this

    Marine, J. C., Topham, D. J., McKay, C., Wang, D., Parganas, E., Stravopodis, D., Yoshimura, A., & Ihle, J. N. (1999). SOCS1 deficiency causes a lymphocyte-dependent perinatal lethality. Cell, 98(5), 609-616. https://doi.org/10.1016/S0092-8674(00)80048-3