Liver degeneration and lymphoid deficiencies in mice lacking suppressor of cytokine signaling-1

Robyn Starr, Donald Metcalf, Andrew G. Elefanty, Marta Brysha, Tracy A. Willson, Nicos A. Nicola, Douglas J. Hilton, Warren S. Alexander

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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.

Original languageEnglish
Pages (from-to)14395-14399
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Volume95
Issue number24
DOIs
Publication statusPublished - 24 Nov 1998
Externally publishedYes

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