N. Patil et al., A POTASSIUM CHANNEL MUTATION IN WEAVER MICE IMPLICATES MEMBRANE EXCITABILITY IN GRANULE CELL-DIFFERENTIATION, Nature genetics, 11(2), 1995, pp. 126-129
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.