Drosophila as a model for epilepsy: bss is a gain-of-function mutation in the para sodium channel gene that leads to seizures.
We report the identification of bang senseless (bss), a Drosophila melanogaster mutant exhibiting seizure-like behaviors, as an allele of the paralytic (para) voltage-gated Na(+) (Na(V)) channel gene. Mutants are more prone to seizure episodes than normal flies because of a lowered seizure threshold. The bss phenotypes are due to a missense mutation in a segment previously implicated in inactivation, termed the "paddle motif" of the Na(V) fourth homology domain. Heterologous expression of cDNAs containing the bss(1) lesion, followed by electrophysiology, shows that mutant channels display altered voltage dependence of inactivation compared to wild type. The phenotypes of bss are the most severe of the bang-sensitive mutants in Drosophila and can be ameliorated, but not suppressed, by treatment with anti-epileptic drugs. As such, bss-associated seizures resemble those of pharmacologically resistant epilepsies caused by mutation of the human Na(V) SCN1A, such as severe myoclonic epilepsy in infants or intractable childhood epilepsy with generalized tonic-clonic seizures.
Department of Environmental Science, Policy and Management, University of California, Berkeley, California 94720, USA. louiseparker@berkeley.edu
Louise
L
Parker
Miguel
M
Padilla
Yuzhe
Y
Du
Ke
K
Dong
Mark A
MA
Tanouye
D000595:Amino Acid Sequence; D000818:Animals; D004195:Disease Models, Animal; D004330:Drosophila / Q000235:genetics / Q000378:metabolism; D055724:Electrophysiological Phenomena / Q000235:genetics; D004827:Epilepsy; D005786:Gene Expression Regulation; D005838:Genotype; D008969:Molecular Sequence Data; D020125:Mutation, Missense; D010641:Phenotype; D012640:Seizures / Q000235:genetics*; D016415:Sequence Alignment; D015222:Sodium Channels / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*
D015222:Sodium Channels