Seizure suppression by shakB2, a gap junction mutation in Drosophila.
Gap junction proteins mediate electrical synaptic transmission. In Drosophila, flies carrying null mutations in the shakB locus, such as shakB2, have behavioral and electrophysiological defects in the giant fiber (GF) system neurocircuit consistent with a loss of transmission at electrical synapses. The shakB2 mutation also affects seizure susceptibility. Mutant flies are especially seizure-resistant and have a high threshold to evoked seizures. In addition, in some double mutant combinations with "epilepsy" mutations, shakB2 appears to act as a seizure-suppressor mutation: shakB2 restores seizure susceptibility to the wild-type range in the double mutant. In double mutant combinations, shakB2 completely suppresses seizures caused by slamdance (sda), knockdown (kdn), and jitterbug (jbug) mutations. Seizures caused by easily shocked (eas) and technical knockout (tko) mutations are partially suppressed by shakB2. Seizures caused by bang-sensitive (bas2) and bang-senseless (bss1, bss2 alleles) mutations are not suppressed by shakB2. These results show the use of Drosophila as a model system for studying the kinds of genetic interactions responsible for seizure susceptibility, bringing us closer to unraveling the complexity of seizure disorders in humans.
Song
Juan
J
Department of Environmental Science, Policy and Management, Division of Insect Biology, University of California, Berkeley, Berkeley, CA 94720, USA. juansong@berkeley.edu
Tanouye
Mark A
MA
D000818:Animals; D030801:Animals, Genetically Modified / Q000235:genetics / Q000378:metabolism; D017630:Connexins / Q000172:deficiency / Q000235:genetics* / Q000378:metabolism; D029721:Drosophila Proteins / Q000172:deficiency / Q000235:genetics* / Q000378:metabolism; D004331:Drosophila melanogaster / Q000235:genetics* / Q000378:metabolism; D017629:Gap Junctions / Q000235:genetics* / Q000378:metabolism; D020022:Genetic Predisposition to Disease / Q000235:genetics; D009154:Mutation; D009419:Nerve Tissue Proteins / Q000172:deficiency / Q000235:genetics* / Q000378:metabolism; D012640:Seizures / Q000235:genetics* / Q000378:metabolism*; D009435:Synaptic Transmission / Q000502:physiology*
D017630:Connexins; D029721:Drosophila Proteins; D009419:Nerve Tissue Proteins; C079324:shakB protein, Drosophila