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.
Metcalf
D
D
The Walter and Eliza Hall Institute of Medical Research and The Cooperative Research Centre for Cellular Growth Factors, Royal Melbourne Hospital, Victoria, Australia.
Greenhalgh
C J
CJ
Viney
E
E
Willson
T A
TA
Starr
R
R
Nicola
N A
NA
Hilton
D J
DJ
Alexander
W S
WS
D000818:Animals; D001835:Body Weight; D016207:Cytokines / Q000378:metabolism; D004268:DNA-Binding Proteins; D005260:Female; D005877:Gigantism / Q000209:etiology* / Q000235:genetics; D007334:Insulin-Like Growth Factor I / Q000502:physiology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D016296:Mutagenesis; D011506:Proteins / Q000235:genetics / Q000502:physiology*; D011995:Recombination, Genetic; D012097:Repressor Proteins; D015398:Signal Transduction; D013234:Stem Cells; D050826:Suppressor of Cytokine Signaling Proteins; D015534:Trans-Activators
D016207:Cytokines; D004268:DNA-Binding Proteins; D011506:Proteins; D012097:Repressor Proteins; C491409:Socs2 protein, mouse; D050826:Suppressor of Cytokine Signaling Proteins; D015534:Trans-Activators; D007334:Insulin-Like Growth Factor I