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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 pathway1. 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.

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Figure 1: Disruption of the SOCS-2 locus by homologous recombination.
Figure 2: Excessive growth of SOCS-2-/- mice.
Figure 3: Pathology in SOCS-2-/- mice.
Figure 4: Deregulated growth hormone signalling in SOCS-2-/- mice.

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We thank N. Sprigg, J. Mighall, S. Mifsud and L. DiRago for technical assistance; K. Hanzinikolas for animal care; S. Mihajlovic for histology; and F. Koentgen, L. Barnett, J. DeWinter and M. Swift of the Walter and Eliza Hall Institute Genetically Modified Mouse Facility and T. Adams for discussions and critical assessment of the manuscript. This work was supported by the National Health and Medical Research Council, Canberra, the Anti-Cancer Council of Victoria, an Australian Government Cooperative Research Centres Program Grant, the National Institutes of Health, Bethesda, the J. D. and L. Harris Trust and AMRAD Operations Pty Ltd, Melbourne.

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Correspondence to Warren S. Alexander.

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Metcalf, D., Greenhalgh, C., Viney, E. et al. Gigantism in mice lacking suppressor of cytokine signalling-2. Nature 405, 1069–1073 (2000).

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