Biology Department, Boston College, Chestnut Hill, Massachusetts 02467, USA.
Epilepsia. 2011 Feb;52(2):347-57. doi: 10.1111/j.1528-1167.2010.02898.x. Epub 2011 Jan 4.
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.
We compared the behavior of EL mice to age-matched 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.
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.
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.
自闭症是一种多因素疾病，涉及社交互动和沟通障碍，以及受限和重复行为。大约 30%的自闭症患者在成年后会发展为癫痫。EL 小鼠长期以来一直被作为具有复杂部分性癫痫发作的多因素特发性全身性癫痫的天然模型进行研究。由于癫痫是自闭症的一种共病特征，我们评估了 EL 小鼠是否存在与自闭症相关的行为。
我们将 EL 小鼠与年龄匹配的对照 DDY 小鼠（一种遗传相关的非癫痫品系）进行比较。在旷场和明暗箱测试中比较了这些小鼠，以测量活动、探索行为以及受限和重复行为。采用食物偏好的社会传递测试评估社交沟通。还评估了 EL 和 DDY 小鼠在其自身笼中的行为，作为重复活动的衡量标准。
我们发现 EL 小鼠表现出几种与自闭症相关的行为异常。EL 小鼠在社交互动和兴趣受限模式方面存在明显缺陷。EL 小鼠的活动、探索行为和受限行为明显多于 DDY 小鼠。EL 小鼠在食物偏好的社会传递测试中表现出障碍。此外，在 EL 小鼠中观察到刻板性肌阵挛跳跃行为，但在 DDY 小鼠中未观察到。有趣的是，在测试后 24 小时内发生的癫痫活动加剧了 EL 小鼠中发现的自闭症行为异常。
这些发现表明，EL 小鼠表现出与自闭症患者相似的行为异常。我们提出 EL 小鼠可以用作自闭症和癫痫的天然模型。
