A POTASSIUM CHANNEL MUTATION IN WEAVER MICE IMPLICATES MEMBRANE EXCITABILITY IN GRANULE CELL-DIFFERENTIATION

Early events in neuronal differentiation are generally considered to b e regulated by factors independent of alterations in membrane permeabi lity. Weaver mice harbour a mutation that blocks neuronal differentiat ion just after cessation of cell division, prior to cell migration and synaptogenesis. Cerebellar granule cells in homozygous weaver mice fa il to differentiate, either because intrinsic cues are absent or becau se the granule cells are unable to respond to those cues. We now repor t that weaver mice have a missense mutation in a gene encoding a G-pro tein coupled inward rectifier potassium channel. The mutation alters t he putative ion-permeable, pore-forming domain of the protein, suggest ing that granule cell differentiation is regulated by changes in membr ane permeability.