Unraveling Genetic Modifiers in the Mouse Model of Absence Epilepsy

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Absence seizures -⁠ also known as “petit-mal” -⁠ define a common form of epilepsy most prevalent in children, but also seen at other ages, and in related diseases such as juvenile myoclonic epilepsy. Absence seizures cause brief periods of unconsciousness, and are accompanied by characteristic abnormal brain waves called “spike-wave discharges” (SWD) due to their appearance in the electroencephalogram (EEG). Although few genes are known for human absence seizures, perhaps because the underlying genetics are complex, several laboratory rodent models exist, including one caused by mutation of a gene called Gria4. While studying Gria4, we noticed that a mouse strain called C3H can suppress or enhance the frequency and severity of Gria4-associated SWD in a perplexing manner; such effects are generally attributed to “modifier” genes. Here we identify a novel modifier –⁠ called “pecanex-like 2”, or Pcnxl2 for short –⁠ that reduces the severity of SWD in the C3H substrain in which the Gria4 mutation originally arose. This finding directed us to use of related substrains to locate additional modifiers, one of which has an even more profound effect on SWD episodes. Modifier genes, nature's way of controlling seizure severity, are promising targets for better understanding seizure mechanisms and potential new therapies in the future.

Vyšlo v časopise: Unraveling Genetic Modifiers in the Mouse Model of Absence Epilepsy. PLoS Genet 10(7): e32767. doi:10.1371/journal.pgen.1004454
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pgen.1004454

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