A spontaneous recurrent seizure-related Rattus NSF gene identified by linker capture subtraction

Spontaneous recurrent seizures (SRS) are the major clinical characteristic of epilepsy. In this study, using a SRS-behavior test combined with linker capture subtraction (LCS) to identify genes altered in their expression in response to a single kainic acid (KA)-induced SRS at 3 weeks in the rat hip pocampal formation. Dot blot analysis of the differentially expressed cDNA fragments with LCS showed the down-regulation of one cDNA related to SRS, w hich was designated epilepsy-related gene 1 (ERG1). Northern blot analysis showed that ERG1 mRNA was reduced by KA administration with and without SRS , but more so with SRS. This differential expression had also been confirme d by in situ hybridization, which showed that ERG1 mRNA was down-regulated in the dorsal dentate granule cells (dDGCs) of the hippocampal formation, b ut remarkable up-regulated in the amygdalohippocampal area (AHi), posterome dial cortical amygdaloid nucleus (PMCo) and perirhinal cortex (PRh). The co mplete cDNA of ERG1 was cloned, sequenced (AF142097). It encodes a Rattus h omologue of N-ethylmaleimide-sensitive fusion protein (NSF), which is an AT Pase that plays a key role in mediating docking and/or fusion of transport vesicles in the multi-step pathways of vesicular transport. Sequence analys is revealed that ERG1 has high sequence similarity with the cDNA of the Mus musculus suppressor of K+ transport growth defect (SKD2), N-ethylmaleimide (NEM)-sensitive fusion protein of Chinese hamster and human NEM-sensitive f actor (HSU03985). (C) 2001 Elsevier Science B.V. All rights reserved.