A potassium channel mutation in weaver mice implicates membrane excitability in granule cell differentiation.
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.
Patil
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N
Department of Genetics, Stanford University Medical School, California 94305-5120, USA.
Cox
D R
DR
Bhat
D
D
Faham
M
M
Myers
R M
RM
Peterson
A S
AS
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002454:Cell Differentiation / Q000235:genetics*; D002531:Cerebellum / Q000166:cytology* / Q000502:physiology; D002874:Chromosome Mapping; D002891:Chromosomes, Human, Pair 21; D003433:Crosses, Genetic; D017931:DNA Primers; D051676:G Protein-Coupled Inwardly-Rectifying Potassium Channels; D019204:GTP-Binding Proteins / Q000502:physiology*; D015870:Gene Expression; D006720:Homozygote; D006801:Humans; D008540:Meiosis; D051379:Mice; D008810:Mice, Inbred C57BL; D008818:Mice, Neurologic Mutants; D008969:Molecular Sequence Data; D009115:Muridae; D009474:Neurons / Q000166:cytology / Q000502:physiology*; D017354:Point Mutation; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D015221:Potassium Channels / Q000737:chemistry / Q000235:genetics* / Q000502:physiology*; D024661:Potassium Channels, Inwardly Rectifying; D017433:Protein Structure, Secondary; D017384:Sequence Deletion; D017386:Sequence Homology, Amino Acid
D017931:DNA Primers; D051676:G Protein-Coupled Inwardly-Rectifying Potassium Channels; D015221:Potassium Channels; D024661:Potassium Channels, Inwardly Rectifying; D019204:GTP-Binding Proteins