A potassium channel mutation in weaver mice implicates membrane excitability in granule cell differentiation
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1Department of Genetics, Stanford University Medical School, California 94305-5120, USA.
Abstract:
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.
Insights
Neuronal differentiation is typically independent of membrane permeability. However, a mutation affecting a potassium channel in weaver mice suggests membrane permeability changes regulate this crucial process.
Area of Science:
- Neuroscience
- Molecular Biology
- Genetics
Background:
- Neuronal differentiation is crucial for brain development.
- Early differentiation events are thought to be independent of membrane permeability.
- The weaver mouse model exhibits a block in neuronal differentiation.
Purpose of the Study:
- To investigate the molecular basis of the differentiation defect in weaver mice.
- To determine if membrane permeability plays a role in neuronal differentiation.
Main Methods:
- Genetic analysis of weaver mice.
- Identification of mutations in genes encoding ion channels.
Main Results:
- Weaver mice possess a missense mutation in a G-protein coupled inward rectifier potassium channel gene.
- The mutation is located in the channel's pore-forming domain.
- This mutation disrupts ion permeability.
Conclusions:
- Granule cell differentiation is regulated by changes in membrane permeability.
- The weaver mutation provides a novel link between ion channel function and neuronal differentiation.