STEEL MUTANT MICE ARE DEFICIENT IN HIPPOCAMPAL LEARNING BUT NOT LONG-TERM POTENTIATION

Mice carrying mutations in either the dominant white-spotting (W) or S teel (Sl) loci exhibit deficits in melanogenesis, gametogenesis, and h ematopoiesis. W encodes the Kit receptor tyrosine kinase, while Sl enc odes the Kit ligand, Steel factor, and the receptor-ligand pair are co ntiguously expressed at anatomical sites expected from the phenotypes of W and Sl mice. The c-kit and Steel genes are also both highly expre ssed in the adult murine hippocampus: Steel is expressed in dentate gy rus neurons whose messy fiber axons synapse with the c-kit expressing CA3 pyramidal neurons. We report here that Sl/Sl(d) mutant mice have a specific deficit in spatial learning. These mutant mice are also defi cient in baseline synaptic transmission between the dentate gyrus and CA3 but show normal long-term potentiation in this pathway. These obse rvations demonstrate a role for Steel factor/Kit signaling in the adul t nervous system and suggest that a severe deficit in hippocampal-depe ndent learning need not be associated with reduced hippocampal long-te rm potentiation.