Department of Anatomy and Cell Biology, University of Melbourne, Melbourne, Victoria 3010, Australia.
Neurogenetics. 2011 Aug;12(3):253-7. doi: 10.1007/s10048-011-0289-2. Epub 2011 Jun 18.
Juvenile mice of the DBA/2J strain undergo generalised seizures when exposed to a high-intensity auditory stimulus. Genetic analysis identified three different loci underlying this audiogenic seizure proneness (ASP)-Asp1, Asp2 and Asp3 on chromosomes 12, 4 and 7, respectively. Asp1 is thought to have the strongest influence, and mice with only Asp1 derived from the DBA/2J strain are reported to exhibit ASP. The aim of this study was to characterise more accurately the contributions of the Asp1 and Asp3 loci in ASP using congenic strains. Each congenic strain contains a DBA/2J-derived interval encompassing either Asp1 or Asp3 on a C57BL/6J genetic background. A double congenic C57BL/6J strain containing both Asp loci derived from DBA/2J was also generated. Here, we report that DBA/2J alleles at both of these Asp loci are required to confer ASP because congenic C57BL/6 mice harbouring DBA/2J alleles at only Asp1 or Asp3 do not exhibit ASP, whereas DBA/2J alleles at both loci resulted in increased susceptibility for audiogenic seizure in double congenic C57BL/6 mice.
幼年 DBA/2J 品系小鼠在受到高强度听觉刺激时会发生全身性癫痫发作。遗传分析确定了三个不同的基因座，分别位于染色体 12、4 和 7 上，这些基因座是导致这种听觉敏感性癫痫易感性（ASP）的原因，分别称为 Asp1、Asp2 和 Asp3。Asp1 被认为影响最大，只从 DBA/2J 品系获得 Asp1 的小鼠被报道表现出 ASP。本研究的目的是使用同基因系更准确地描述 Asp1 和 Asp3 基因座在 ASP 中的作用。每个同基因系都包含一个源自 C57BL/6J 遗传背景的 DBA/2J 衍生区间，分别包含 Asp1 或 Asp3。还生成了一个包含两个 Asp 基因座的 DBA/2J 衍生片段的双同基因 C57BL/6J 品系。在这里，我们报告称，这两个 Asp 基因座的 DBA/2J 等位基因都需要赋予 ASP，因为仅在 Asp1 或 Asp3 上携带 DBA/2J 等位基因的同基因 C57BL/6 小鼠不会表现出 ASP，而两个基因座上的 DBA/2J 等位基因导致双同基因 C57BL/6 小鼠对听觉性癫痫发作的敏感性增加。
