The EL mouse: A natural model of autism and epilepsy

Abstract

SUMMARYPurpose: Autism is a multifactorial disorder that involves impairments in social interactions and communication, as well as restricted and repetitive behaviors. About 30% of individuals with autism develop epilepsy by adulthood. The EL mouse has long been studied as a natural model of multifactorial idiopathic generalized epilepsy with complex partial seizures. Because epilepsy is a comorbid trait of autism, we evaluated the EL mouse for behaviors associated with autism. Methods: We compared the behavior of EL mice to agematched control DDY mice, a genetically related nonepileptic strain. The mice were compared in the open field and in the light-dark compartment tests to measure activity, exploratory behavior, and restricted and repetitive behaviors. The social transmission of food preference test was employed to evaluate social communication. Home-cage behavior was also evaluated in EL and DDY mice as a measure of repetitive activity.Key Findings: We found that EL mice displayed several behavioral abnormalities characteristic of autism. Impairments in social interaction and restricted patterns of interest were evident in EL mice. Activity, exploratory behavior, and restricted behavior were significantly greater in EL mice than in DDY mice. EL mice exhibited impairment in the social transmission of food preference assay. In addition, a stereotypic myoclonic jumping behavior was observed in EL mice, but was not seen in DDY mice. It is of interest to note that seizure activity within 24 h of testing exacerbated the autistic behavioral abnormalities found in EL mice. Significance: These findings suggest that the EL mouse expresses behavioral abnormalities similar to those seen in persons with autism. We propose that the EL mouse can be utilized as a natural model of autism and epilepsy.

Ketogenic diets improve behaviors associated with autism spectrum disorder in a sex-specific manner in the EL mouse

“…These findings are consistent with previous work characterizing EL mice as having low or abnormal sociability in various other paradigms [50,61–63]. Notably, after KD feeding, females became highly social in the 3-chamber test; there was moderately increased sociability in males.…”

“…Here we tested the effects of KDs on behavior and blood chemistry in both sexes of EL mice, an idiopathic model of comorbid epilepsy [49] and ASD [50]. EL mice mimic human autism in that the etiology is unknown and the pathology develops gradually after birth, and complement other mouse ASD models by also developing seizures, a common comorbidity in patients.…”

Autism Spectrum Disorders: Translating human deficits into mouse behavior

“…Initially developed by Bennett Galef (Galef, 1983), the social transmission of food preference test is an intriguing olfactory and memory task with increasing importance in establishing autistic-like features in mice (Meidenbauer et al, 2011;Ryan et al, 2008). In this task the subject mouse interacts with a cage mate (the demonstrator mouse) that has been fed with a novel flavored food (Fig.…”

Reduced glucose utilization underlies seizure protection with dietary therapy in epileptic EL mice

“…Our goal was to evaluate the acute roles of glucose and β-hydroxybutyrate (the major circulating ketone body) in conferring seizure protection to the EL mouse, a model of multifactorial idiopathic generalized epilepsy [13–15]. Seizures in EL mice can be managed through AED and dietary therapy, which makes the EL mouse an ideal model to study the mechanisms through how seizure protection is conferred [5, 6, 16, 17].…”