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Title: Synthetic Lethal Interaction Between ether-a-go-go Shaker and escargot Mutations in Drosophila
Authors: Zhang, Samantha Liang
Issue Date: 6-Jul-2007
Abstract: Escargot (esg) is a member of the snail family of transcription factors. Gain-of-function esg mutantions have been identified in previous studies as strong suppressors of seizure behavior in Drosophila models for epilepsy (Hekmat-Scafe et al. 2005). Recently, during a screen utilizing the ether-a- go-go (eag) Shaker (Sh) double mutant to identify genes that affect oxidative stress sensitivity, we uncovered a lethal interaction between gain-of-function esg mutations and the eag Sh double mutant The eag and Sh genes encode potassium channel subunits; epilepsy studies have revealed that eag and Sh are also mild seizure suppressors (Kuebler et al. 2001). The esg gene interaction is thus of great interest as it rescues seizure prone mutations while causing lethality in animals with increased seizure resistance. This study investigates the lethal interaction between eag Sh and esg to better understand its underlying mechanisms. Our results indicate that lethality is caused by severely impaired motor control in the adult. The animal exhibits many adult specific phenotypes, with distinctive synaptic phenotypes in adult and larvae. These results suggest that the critical period for esg-induced lethality is during adult development which agrees with the results of epilepsy studies.
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