It is becoming increasingly clear that the genetic background of mice and rats, even in inbred strains, can have a profound influence on measures of seizure susceptibility and epilepsy. These differences can be capitalized upon through genetic mapping studies to reveal genes important for seizures and epilepsy. However, strain background and particularly mixed genetic backgrounds of transgenic animals need careful consideration in both the selection of strains and in the interpretation of results and conclusions. For instance, mice with targeted deletions of genes involved in epilepsy can have profoundly disparate phenotypes depending on the background strain. In this review, we discuss findings related to how this genetic heterogeneity has and can be utilized in the epilepsy field to reveal novel insights into seizures and epilepsy. Moreover, we discuss how caution is needed in regards to rodent strain or even animal vendor choice, and how this can significantly influence seizure and epilepsy parameters in unexpected ways. This is particularly critical in decisions regarding the strain of choice used in generating mice with targeted deletions of genes. Finally, we discuss the role of environment (at vendor and/or laboratory) and epigenetic factors for inter- and intrastrain differences and how such differences can affect the expression of seizures and the animals' performance in behavioral tests that often accompany acute and chronic seizure testing.

译文

越来越清楚的是,即使在近交品系中,小鼠和大鼠的遗传背景也可能对癫痫发作易感性和癫痫的测量产生深远的影响。这些差异可以通过基因图谱研究来利用,以揭示对癫痫发作和癫痫重要的基因。然而,在菌株的选择以及结果和结论的解释中,需要仔细考虑菌株的背景,尤其是转基因动物的混合遗传背景。例如,根据背景菌株,具有与癫痫有关的基因靶向缺失的小鼠可能具有截然不同的表型。在这篇综述中,我们讨论了与这种遗传异质性如何具有并可以在癫痫领域中使用的发现,以揭示对癫痫发作和癫痫的新见解。此外,我们讨论了在啮齿动物菌株甚至动物供应商的选择方面如何谨慎,以及这如何以意想不到的方式显着影响癫痫发作和癫痫参数。这在决定用于产生具有靶向基因缺失的小鼠的选择菌株方面尤为重要。最后,我们讨论环境 (在供应商和/或实验室) 和表观遗传因素对菌株间和内差异的作用,以及这些差异如何影响癫痫发作的表达和动物在行为测试中的表现,通常伴随急性和慢性癫痫发作测试。

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