Lorenzana Ariana, Chancer Zackary, Schauwecker P Elyse
Department of Cell and Neurobiology, University of Southern California Keck School of Medicine, Los Angeles, CA 90089, USA.
Eur J Neurosci. 2007 Apr;25(7):1998-2008. doi: 10.1111/j.1460-9568.2007.05443.x.
C57BL/6J (B6) and FVB/NJ (FVB) mice are phenotypically distinct in their susceptibility to seizure-induced cell death after kainate administration. Previous studies using quantitative trait loci (QTLs) mapping established that the distal region of mouse chromosome 18 contains a gene(s) that is probably responsible for the difference in seizure-induced cell death susceptibility between two inbred strains, B6 and FVB, that are relatively resistant and susceptible, respectively, to seizure-induced cell death. The genetic locus has been mapped to a approximately 12-centimorgan region of chromosome 18, designated as seizure-induced cell death 1 (Sicd1). In order to confirm the Sicd1 QTL, we have developed congenic mouse strains containing the relevant donor segment from the resistant B6 strain on the susceptible FVB background, also referred to as the FVB.B6-Sicd1 congenic strain. Congenic and FVB littermate controls were tested in a seizure-induced cell death paradigm. The presence of B6 chromosome 18 alleles on an FVB genetic background conferred protection against seizure-induced cell death, as compared with FVB littermate controls. To further localize the Sicd1 QTL, new congenic lines carrying overlapping intervals of the B6 segment were created [interval-specific congenic lines (ISCLs)-1-4] and assessed for seizure-induced cell death phenotype. All of the ISCLs exhibited reduced cell death associated with the B6 phenotype, as compared with the parental FVB strain. The most dramatic of these, ISCL-4, showed a nearly four-fold reduction in the extent of seizure-induced cell death. This suggests that ISCL-4 contains the putative gene(s) of the Sicd1 QTL.
C57BL/6J（B6）小鼠和FVB/NJ（FVB）小鼠在给予海藻酸后对癫痫诱导的细胞死亡的易感性方面表现出明显的表型差异。先前使用数量性状基因座（QTL）定位的研究表明，小鼠18号染色体的远端区域包含一个基因，该基因可能是导致两个近交系B6和FVB在癫痫诱导的细胞死亡易感性上存在差异的原因，这两个近交系分别对癫痫诱导的细胞死亡相对具有抗性和易感性。该基因座已被定位到18号染色体上大约12厘摩的区域，命名为癫痫诱导细胞死亡1（Sicd1）。为了确认Sicd1 QTL，我们培育了携带来自抗性B6品系相关供体片段的近交系小鼠，其背景为易感的FVB，也称为FVB.B6-Sicd1近交系。在癫痫诱导的细胞死亡模型中对近交系和FVB同窝对照进行了测试。与FVB同窝对照相比，FVB遗传背景上存在B6 18号染色体等位基因可提供对癫痫诱导细胞死亡的保护。为了进一步定位Sicd1 QTL，创建了携带B6片段重叠区间的新近交系[区间特异性近交系（ISCLs）-1-4]，并评估其癫痫诱导细胞死亡表型。与亲代FVB品系相比，所有ISCLs均表现出与B6表型相关的细胞死亡减少。其中最显著的ISCL-4在癫痫诱导细胞死亡程度上显示出近四倍的降低。这表明ISCL-4包含Sicd1 QTL的推定基因。
