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Gigantism in mice lacking suppressor of cytokine signalling-2

D Metcalf1, C J Greenhalgh, E Viney

  • 1The Walter and Eliza Hall Institute of Medical Research and The Cooperative Research Centre for Cellular Growth Factors, Royal Melbourne Hospital, Victoria, Australia.

Nature
|July 13, 2000
PubMed

Insights

Suppressor of cytokine signalling-2 (SOCS-2) deficiency in mice leads to significantly larger body size and organ growth. This suggests SOCS-2 plays a crucial role in regulating growth hormone and insulin-like growth factor-I signaling pathways.

Area of Science:

  • Molecular Biology
  • Genetics
  • Endocrinology

Background:

  • Suppressor of cytokine signalling-2 (SOCS-2) is part of a protein family that negatively regulates cytokine signaling.
  • It inhibits the Janus kinase (JAK)/signal transducers and activators of transcription (STAT) pathway.

Purpose of the Study:

  • To investigate the in vivo function of SOCS-2.
  • To determine the role of SOCS-2 in growth regulation.

Main Methods:

  • Utilized genetically modified mice lacking SOCS-2 expression (SOCS-2-/-).
  • Compared growth parameters and physiological characteristics between SOCS-2-/- and wild-type littermates.

Main Results:

  • SOCS-2-/- mice exhibited significantly increased body weight and long bone length post-weaning.
  • Enlargement of most organs was observed in SOCS-2 deficient mice.
  • Evidence of deregulated growth hormone and insulin-like growth factor-I (IGF-I) signaling was found, including altered protein production and local IGF-I levels.

Conclusions:

  • SOCS-2 plays an essential negative regulatory role in the growth hormone/IGF-I signaling pathway.
  • Loss of SOCS-2 function results in enhanced growth and organ size.

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