Lack of Socs2 expression causes the high-growth phenotype in mice

Characterizing causal molecular defects in mouse models of overgrowth or dw arfism helps to identify the key genes and pathways that regulate the growt h process. We report here the molecular basis for high growth (hg), a spont aneous mutation that causes a 30-50% increase in postnatal growth. We concl ude 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 dem onstrate 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 g rowth prenatally and postnatally most likely through deregulating the growt h hormone (GH)/insulin-like growth factor I (IGF1), These results demonstra te a critical role for Socs2 in controlling growth, (C) 2001 Academic Press .