Lack of Socs2 expression causes the high-growth phenotype in mice.
Characterizing causal molecular defects in mouse models of overgrowth or dwarfism helps to identify the key genes and pathways that regulate the growth process. We report here the molecular basis for high growth (hg), a spontaneous mutation that causes a 30-50% increase in postnatal growth. We conclude that hg is an allele of the suppressor of cytokine signaling 2 (Socs2), a member of a family of regulators of cytokine signal transduction. We demonstrate mapping of Socs2 to the hg region, lack of Socs2 mRNA expression, a disruption of the Socs2 locus in high-growth (HG) mice, and a similarity of phenotypes of HG mice and Socs2(-/-) mice generated by gene targeting. Characteristics of the HG phenotype suggest that Socs2 deficiency affects growth prenatally and postnatally most likely through deregulating the growth hormone (GH)/insulin-like growth factor I (IGF1). These results demonstrate a critical role for Socs2 in controlling growth.
Horvat
S
S
Roslin Institute (Edinburgh), Roslin, EH25 9PS, Scotland, UK. simon.horvat@bfro.uni-lj.sl
Medrano
J F
JF
D000818:Animals; D016207:Cytokines / Q000378:metabolism; D004268:DNA-Binding Proteins; D006128:Growth / Q000235:genetics / Q000502:physiology*; D006130:Growth Disorders / Q000235:genetics; D006801:Humans; D051379:Mice; D008969:Molecular Sequence Data; D009154:Mutation; D010641:Phenotype; D011506:Proteins / Q000235:genetics / Q000502:physiology*; D012097:Repressor Proteins; D015398:Signal Transduction; D050826:Suppressor of Cytokine Signaling Proteins; D015534:Trans-Activators
D016207:Cytokines; D004268:DNA-Binding Proteins; D011506:Proteins; D012097:Repressor Proteins; C106643:SOCS2 protein, human; C491409:Socs2 protein, mouse; D050826:Suppressor of Cytokine Signaling Proteins; D015534:Trans-Activators