The genetic audiogenic seizure hamster from Salamanca: The GASH:Sal

Abstract

The hamster has been previously described as a paroxysmal dystonia model, but our strain is currently recognized as a model of audiogenic seizures (AGS). The original first epileptic hamster appeared spontaneously at the University of Valladolid, where it was known as the GPG:Vall line, and was transferred to the University of Salamanca where a new strain was developed, named GASH:Sal. By testing auditory brainstem responses, the GASH:Sal exhibits elevated auditory thresholds that indicate a hearing impairment. Moreover, amplified fragment length polymorphism analysis distinguished genetic differences between the susceptible GASH:Sal hamster strain and the control Syrian hamsters. The GASH:Sal constitutes an experimental model of reflex epilepsy of audiogenic origin derived from an autosomal recessive disorder. Thus, the GASH:Sal exhibits generalized tonic-clonic seizures, characterized by a short latency period after auditory stimulation, followed by wild running, a convulsive phase, and finally stupor, with origin in the brainstem. The seizure profile of the GASH:Sal is similar to those exhibited by other models of inherited AGS susceptibility, which decreases after six months of age, but the proneness across generations is maintained. The GASH:Sal can be considered a reliable model of audiogenic seizures, suitable to investigate current antiepileptic pharmaceutical treatments as well as novel therapeutic drugs.This article is part of a Special Issue entitled Genetic Models-Epilepsy.

Analysis of gene variants in the GASH/Sal model of epilepsy

“…To identify gene variants possibly implicated in the development of audiogenic seizures in the GASH/Sal strain, additional selection criteria were defined and applied to focus our study on the variants that are most likely to be involved in the phenotype of our experimental model. These criteria include the presence of homozygous mutations in GASH/Sal animals, because susceptibility is inherited in an autosomal recessive inheritance pattern [24], the existence of similar mutations related to the development of seizures or different types of epilepsy, in both humans and animal models, and the lack of duplicates and adequate coverage. After applying these criteria, 22 qualifying variants were selected, namely 7 high-and 15 moderate-impact variants ( Table 1).…”

“…In all these models, different types of studies on seizures and pharmacological treatments have been conducted in the inferior colliculus as an epileptogenic nucleus and in auditory pathways [31,[74][75][76][77][78]. In the GASH/Sal model, previous studies have determined that susceptibility to developing the epileptic phenotype shows an autosomal recessive inheritance pattern [24]. A recent study, which analyzed the transcriptome of the WAR model, highlighted changes in the expression of 64 genes after audiogenic stimulation, thereby identifying new genes involved in the epileptic phenotype [79].…”

“…The genetic audiogenic seizure hamster from Salamanca (GASH/Sal) is a genetic model of audiogenic seizures derived from an autosomal recessive disorder. The GASH/Sal model exhibits generalized tonic-clonic audiogenic seizures induced by high-intensity acoustic stimulation, mimicking those sensory-evoked reflex seizures seen in humans [24]. This animal model of epilepsy has the potential to offer innate susceptibility to the development of convulsive seizures in response to acoustic stimuli, without genetic or chemical manipulation, in contrast to other models, which only enable epilepsy studies in the context of the effects of a knocked gene of interest.…”

Top Common Differentially Expressed Genes in the Epileptogenic Nucleus of Two Strains of Rodents Susceptible to Audiogenic Seizures: WAR and GASH/Sal

“…The Wistar Audiogenic Rat (WAR) and the Genetic Audiogenic Seizure Hamster from Salamanca (GASH/Sal) strains are the most recent audiogenic models in rodents (8,9). Although they originate from different species, the WAR and GASH/Sal strains present common aspects.…”

“…Although they originate from different species, the WAR and GASH/Sal strains present common aspects. Both are genetic models sensitive to sound stimuli, the WAR strain developed by selective reproduction of Wistar animals and the GASH/Sal strain with DNA mutations arising in a colony of Syrian hamsters (8,9). During acoustic stimulation (sound intensity 110-120 dB), WAR and GASH/Sal animals exhibit a latency period that is interrupted by a wild running and subsequent generalized tonic-clonic seizures that may progress to more severe motor manifestations, such as dorsoventral flexion of the neck and hyperextension of the forelimbs and hindlimbs (8,9).…”