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 th e negative regulation of cytokine action through inhibition of the Janus ki nase (JAK) signal transducers and activators of transcription (STAT) signal -transduction pathway(1). Here we use mice unable to express SOCS-2 to exam ine its function in vivo. SOCS-2(-/-) mice grew significantly larger than t heir wild-type littermates. Increased body weight became evident after wean ing and was associated with significantly increased long bone lengths and t he proportionate enlargement of most organs. Characteristics of deregulated growth hormone and insulin-like growth factor-I (IGF-I) signalling, includ ing decreased production of major urinary protein, increased local IGF-I pr oduction, and collagen accumulation in the dermis, were observed in SOCS-2- deficient mice, indicating that SOCS-2 may have an essential negative regul atory role in the growth hormone/IGF-I pathway.