Genetic and phenotypic analysis of seizure susceptibility in PL/J mice.
Genetic and phenotypic analysis of seizure susceptibility in PL/J mice.
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PL/J 小鼠癫痫易感性的遗传和表型分析。
DOI：
10.1007/s00335-004-3007-7
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发表时间：
2004
期刊：
影响因子：
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通讯作者：
Nadeau,JosephH
中科院分区：
文献类型：
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作者：
Kitami,Toshimori;Ernest,Sheila;Gallaugher,Laura;Friedman,Lee;Frankel,WayneN;Nadeau,JosephH
癫痫是人类最常见但遗传复杂的神经系统疾病之一。识别能够再现人类癫痫的动物模型对于抗惊厥药物的药理学研究、癫痫的分子和生化发病机制的剖析以及癫痫易感基因的发现具有重要意义。我们发现，PL/J近交系小鼠品系是容易处理和有节奏的投掷诱导癫痫发作。诱导后观察到的强直阵挛性和全身性癫痫发作伴有异常EEG，与EL和SWXL-4小鼠中观察到的癫痫发作相似。PL/J小鼠也有一个极低的阈值电惊厥发作相比，其他菌株，并表现出可变的敏感性戊四唑诱导的癫痫发作。在PL/J小鼠中未发现大体神经结构异常。与抗癫痫的C57 BL/6 J品系杂交显示了低频率节律性癫痫发作特征的半显性遗传。F_2代表明PL/J家系癫痫易感性的遗传为非孟德尔遗传。将对节律性惊厥有抵抗力但对听源性惊厥敏感的DBA/2 J小鼠与PL/J小鼠杂交，发现（DBA/2 J × PL/J）F1小鼠的惊厥发作频率与（C57 BL/6 J × PL/J）F1小鼠相似，但（DBA/2 J × PL/J）F1小鼠的惊厥发作频率和严重程度均高于（C57 BL/6 J × PL/J）F1小鼠。PL/J株是研究癫痫遗传学、神经生物学和药理学的一个有趣的新模型。
Epilepsy is one of the most common but genetically complex neurological disorders in humans. Identifying animal models that recapitulate human epilepsies is important for pharmacological studies of anticonvulsants, dissection of molecular and biochemical pathogenesis of epilepsy, and discovery of epilepsy susceptibility genes. We discovered that the PL/J inbred mouse strain is susceptible to handling- and rhythmic tossing–induced seizure. The tonic–clonic and generalized seizures observed after induction were accompanied by abnormal EEGs, similar to seizures observed in EL and SWXL-4 mice. PL/J mice also had an extremely low threshold to electroconvulsive seizures compared to other strains and showed variable sensitivity to pentylenetetrazole-induced seizures. Gross neurostructural abnormalities were not found in PL/J mice. Crosses with the seizure-resistant C57BL/6 J strain revealed semidominant inheritance of the rhythmic tossing seizure trait with low penetrance. F2 progeny indicated that the genetic inheritance of seizure susceptibility in PL/J is non-Mendelian. We crossed DBA/2 J mice, which are resistant to rhythmic tossing seizure but susceptible to audiogenic seizures, to PL/J. We found that seizure penetrance in (DBA/2 J × PL/J)F1 mice was similar to the penetrance in (C57BL/6 J × PL/J)F1 mice but the severity and frequency of seizure were higher in (DBA/2 J × PL/J)F1 mice. The PL/J strain serves as an interesting new model for studying the genetics, neurobiology, and pharmacology of epilepsy.