Ron-mediated cytoplasmic signaling is dispensable for viability but is required to limit inflammatory responses

Ron receptor activation induces numerous cellular responses in vitro, inclu ding proliferation, dissociation, and migration. Ron is thought to be invol ved in blood cell development in vivo, as well as in many aspects of the im mune response including macrophage activation, antigen presentation, and ni tric oxide regulation. In previous studies to determine the function of Ron in vivo, mice were generated with a targeted deletion of the extracellular and transmembrane regions of this gene. Mice homologous for this deletion appear to die early during embryonic development. To ascertain the in vivo function of Ron in more detail, we have generated mice with a germline abla tion of the tyrosine kinase domain. Strikingly, our studies indicate that t his domain of Ron, and therefore Ron cytoplasmic signaling, is not essentia l for embryonic development. While mice deficient in this domain are overtl y normal, mice lacking Ron signaling have an altered ability to regulate ni tric oxide levels and, in addition, have enhanced tissue damage following a cute and cell-mediated inflammatory responses.