DISRUPTION OF THE JAK1 GENE DEMONSTRATES OBLIGATORY AND NONREDUNDANT ROLES OF THE JAKS IN CYTOKINE-LNDUCED BIOLOGIC RESPONSES

Herein we report the generation of mice lacking the ubiquitously expre ssed Janus kinase, Jak1. Jak1(-/-) mice are runted at birth, fail to n urse, and die perinatally. Although Jak1(-/-) cells are responsive to many cytokines, they fail to manifest biologic responses to cytokines that bind to three distinct families of cytokine receptors. These incl ude all class II cytokine receptors, cytokine receptors that utilize t he gamma(c) subunit for signaling, and the family of cytokine receptor s that depend on the gp130 subunit for signaling. Our results thus dem onstrate that Jak1 plays an essential and nonredundant role in promoti ng biologic responses induced by a select subset of cytokine receptors , including those in which Jak utilization was thought to be nonspecif ic.