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Gigantism in mice lacking suppressor of cytokine signalling-2.

Suppressor of cytokine signalling-2 (SOCS-2) is a member of the suppressor of cytokine signalling family, a group of related proteins implicated in the negative regulation of cytokine action through inhibition of the Janus kinase (JAK) signal transducers and activators of transcription (STAT) signal-transduction pathway. Here we use mice unable to express SOCS-2 to examine its function in vivo. SOCS-2(-/-) mice grew significantly larger than their wild-type littermates. Increased body weight became evident after weaning and was associated with significantly increased long bone lengths and the proportionate enlargement of most organs. Characteristics of deregulated growth hormone and insulin-like growth factor-I (IGF-I) signalling, including decreased production of major urinary protein, increased local IGF-I production, and collagen accumulation in the dermis, were observed in SOCS-2-deficient mice, indicating that SOCS-2 may have an essential negative regulatory role in the growth hormone/IGF-I pathway.

Pubmed ID: 10890450

Authors

  • Metcalf D
  • Greenhalgh CJ
  • Viney E
  • Willson TA
  • Starr R
  • Nicola NA
  • Hilton DJ
  • Alexander WS

Journal

Nature

Publication Data

June 29, 2000

Associated Grants

None

Mesh Terms

  • Animals
  • Body Weight
  • Cytokines
  • DNA-Binding Proteins
  • Female
  • Gigantism
  • Insulin-Like Growth Factor I
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mutagenesis
  • Proteins
  • Recombination, Genetic
  • Repressor Proteins
  • Signal Transduction
  • Stem Cells
  • Suppressor of Cytokine Signaling Proteins
  • Trans-Activators