Nature Genetics
11, 126 - 129 (1995)
doi:10.1038/ng1095-126
A potassium channel mutation in weaver mice implicates membrane excitability in granule cell differentiationNila Patil1, David R. Cox1, Deepti Bhat2, Malek Faham3, Richard M. Myers1
& Andrew S. Peterson2
1Department of Genetics, Stanford University Medical School, Stanford, California 94305-5120, USA
2Departments of Genetics and Neurobiology, Duke University Medical Center, Durham, North Carolina 27710, USA
3Department of Biochemistry and Biophysics, University of California at San Francisco, San Francisco, California 94305-5120, USA Early events in neuronal differentiation are generally considered to be regulated by factors independent of alterations in membrane permeability. Weaver mice harbour a mutation that blocks neuronal differentiation just after cessation of cell division, prior to cell migration and synaptogenesis. Cerebellar granule cells in homozygous weaver mice fail to differentiate, either because intrinsic cues are absent or because the granule cells are unable to respond to those cues. We now report that weaver mice have a missense mutation in a gene encoding a G−protein coupled inward rectifier potassium channel. The mutation alters the putative ion−permeable, pore−forming domain of the protein, suggesting that granule cell differentiation is regulated by changes in membrane permeability.
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