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Mutations of the Calcium Channel Gene cacophony Suppress Seizures in Drosophila

Mutations of the Calcium Channel Gene cacophony Suppress Seizures in Drosophila
Bang sensitive (BS) Drosophila mutants display characteristic seizure-like phenotypes resembling, in some aspects, those of human seizure disorders such as epilepsy. The BS mutant parabss1, caused by a gain-of-function mutation of the voltage-gated Na+ channel gene, is extremely seizure-sensitive with phenotypes that have proven difficult to ameliorate by anti-epileptic drug feeding or by seizure-suppressor mutation. It has been presented as a model for intractable human epilepsy. Here we show that cacophony (cacTS2), a mutation of the Drosophila presynaptic Ca++ channel α1 subunit gene, is a particularly potent seizure-suppressor mutation, reverting seizure-like phenotypes for parabss1 and other BS mutants. Seizure-like phenotypes for parabss1 may be suppressed by as much as 90% in double mutant combinations with cacTS2. Unexpectedly, we find that parabss1 also reciprocally suppresses cacTS2 seizure-like phenotypes. The cacTS2 mutant displays these seizure-like behaviors and spontaneous high-frequency action potential firing transiently after exposure to high temperature. We find that this seizure-like behavior in cacTS2 is ameliorated by 85% in double mutant combinations with parabss1.
- University of California System United States
- University of California, Berkeley United States
- Government of the United States of America United States
- Florey Institute of Neuroscience and Mental Health Australia
- University of California at Berkeley, Department of Molecular and Cell Biology United States
Neurodegenerative, QH426-470, Seizures, Genetics, 2.1 Biological and endogenous factors, Animals, Drosophila Proteins, Humans, Aetiology, Epilepsy, Animal, Neurosciences, Biological Sciences, Brain Disorders, Disease Models, Animal, Phenotype, Neurological, Disease Models, Mutation, Calcium, Calcium Channels, Developmental Biology, Research Article
Neurodegenerative, QH426-470, Seizures, Genetics, 2.1 Biological and endogenous factors, Animals, Drosophila Proteins, Humans, Aetiology, Epilepsy, Animal, Neurosciences, Biological Sciences, Brain Disorders, Disease Models, Animal, Phenotype, Neurological, Disease Models, Mutation, Calcium, Calcium Channels, Developmental Biology, Research Article
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