Development of Hydrocephalus in Mice Lacking SOCS7

SOCS7 is a member of the suppressor of cytokine signaling (SOCS) family of proteins (SOCS1-SOCS7 and CIS). SOCS proteins are composed of an N-terminal domain of variable length, a central Src homology 2 domain, and a C-terminal SOCS box. Biochemical and genetic studies have revealed that SOCS1, SOCS2, SOCS3, and CIS play an important role in the termination of cytokine and growth factor signaling. However, the biological actions of other SOCS proteins are less well defined. To investigate the physiological role of SOCS7, we have used gene targeting to generate mice that lack expression of the Socs7 gene. Socs7-/- mice were born in expected numbers, were fertile, and did not exhibit defects in hematopoiesis or circulating glucose or insulin concentrations. However, Socs7-/- mice were 7-10% smaller than their wild-type littermates, and within 15 weeks of age ≈50% of the Socs7-/- mice died as a result of hydrocephalus that was characterized by cranial distortion, dilation of the ventricular system, reduced thickness of the cerebral cortex, and disorganization of the subcommissural organ. In situ hybridization studies revealed prominent expression of Socs7 in the brain, suggestive of an important functional role of SOCS7 in this organ.