Wang X J, Reynolds E R, Déak P, Hall L M
Department of Biochemical Pharmacology, State University of New York at Buffalo 14260-1200, USA.
J Neurosci. 1997 Feb 1;17(3):882-90. doi: 10.1523/JNEUROSCI.17-03-00882.1997.
Mutations in the seizure (sei) locus cause temperature-induced hyperactivity, followed by paralysis. Gene cloning studies have established that the seizure gene product is the Drosophila homolog of HERG, a member of the eag family of K+ channels implicated in one form of hereditary long QT syndrome in humans. A series of five null alleles with premature stop codons are all recessive, but viable. A missense mutation in the sei gene, which changes the charge at a conserved glutamate residue near the outer mouth of the pore, has a semidominant phenotype, suggesting that the mutant seizure protein acts as a poison in a multimeric complex. Transformation rescue of a null allele with a cDNA under the control of an inducible promoter demonstrates that induced expression of seizure potassium channels in adults rescues the paralytic phenotype. This rescue decays with a t1/2 of approximately 1-1.5 d after gene induction is discontinued, providing the first estimate of ion channel stability in an intact, multicellular animal.
癫痫(sei)位点的突变会导致温度诱导的多动,随后出现麻痹。基因克隆研究表明,癫痫基因产物是HERG的果蝇同源物,HERG是一种K+通道的eag家族成员,与人类一种遗传性长QT综合征有关。一系列带有过早终止密码子的五个无效等位基因都是隐性的,但可存活。sei基因中的一个错义突变改变了孔外口附近保守谷氨酸残基的电荷,具有半显性表型,这表明突变的癫痫蛋白在多聚体复合物中起毒性作用。用诱导型启动子控制下的cDNA对无效等位基因进行转化拯救表明,在成虫中诱导癫痫钾通道的表达可拯救麻痹表型。在基因诱导停止后,这种拯救以约1 - 1.5天的半衰期衰减,这为完整多细胞动物中离子通道稳定性提供了首次估计。