Survey of the genetic modifier for Dravet syndrome

作为Dravet综合征的模型小鼠，在我们的实验室中研究了在Scn 1a基因中引入R1407 X突变的Nav1.1缺陷小鼠（C57 BL/6 J背景）（Ogiwara等人，J Neurosci 27：5903-5914，2007.杂合子小鼠（Scn 1a +/-）表现出自发性癫痫发作，其中约60%存活至成年。有趣的是，杂合子小鼠的存活率取决于小鼠品系。猝死潜伏期的应变依赖性表明，遗传背景携带显性修饰等位基因在一个或多个基因座，决定癫痫表型的严重程度。在这项研究中，以确定修饰基因，我们进行了遗传作图的猝死表型使用回交MSM/Ms株。结果表明，2类修饰基因参与癫痫死亡的发生。1、<st>对猝死高度敏感的修饰基因位于X染色体上。由于与MSM/Ms小鼠回交增加了每一代的存活率，我们估计MSM/Ms品系的常染色体也具有抵抗癫痫症状的2^<nd>修饰基因。

As a model mouse for Dravet syndrome, the Nav1.1 deficient mouse(C57BL/6J background) that introduced R1407X mutation in the Scn1a gene has been investigated in our laboratory(Ogiwara et al., J Neurosci 27 : 5903-5914, 2007. Heterozygous mice(Scn1a+/-) exhibit spontaneous seizures, and approximately 60% of them survive to adulthood. Interestingly, this survivability of heterozygous mice depended on mouse strain. The strain dependency of latency of sudden death indicates that genetic background carries dominant modifier alleles at one or more loci that determine the severity of the epilepsy phenotype. In this study, to identify modifier genes, we performed genetic mapping of the sudden death phenotype using backcrossing to MSM/Ms strain. The results show 2 types of modifier genes involve in mortality induced by epilepsy. 1^<st> modifier gene that is highly sensitive to the sudden death is located on chromosome X. Because backcrossing with MSM/Ms mice increased survival rate in each generation, we estimated that the autosomes of MSM/Ms strain have 2^<nd> modifier gene(s) to resist symptoms of epilepsy also.