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Increased Go activity in C57Bl/6J mice enhances sensitivity to a model of epilepsy
Author(s) -
Kehrl Jason,
Dalton Hans,
Kohut Kevin,
Stern Matt,
Neubig Richard
Publication year - 2013
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.27.1_supplement.660.1
Subject(s) - epilepsy , kindling , kindling model , in vivo , protein subunit , chemistry , pharmacology , biology , medicine , neuroscience , genetics , biochemistry , gene
Many patients suffering from temporal lope epilepsy (TLE) are refractory. This work focused on understanding two potential new therapeutic targets, the hetero‐trimeric G‐proteins G o and G i2 . We hypothesized that increasing activity of these proteins would be protective from seizures as inhibition of these proteins enhances seizure susceptibility. Mouse lines were created with increased activity of G o (Gα o RGSi) or G i2 (Gα i2 RGSi) through the introduction of a point mutation in the α subunit. Both mouse lines were exposed to a chemical kindling model with relevance to TLE. C57Bl/6J Gα o +/RGSi mice have a faster onset to seizure while Gα i2 +/RGSi mice have no change compared to controls. 129SvImJ Gα o +/RGSi mice however, kindle no faster than controls. Furthermore, a 129 modifier region on Chromosome 17 reduces the rate at which B6 Gα o +/RGSi mice kindle. Here we have demonstrated an in vivo role for G o and a novel modifier region in regulating susceptibility to a kindling model of epilepsy however we have yet to identify if these effects are through developmental or acute signaling changes. Supported by NIH grant RO1‐GM39561 (RRN), 5T32GM008322–19 (JMK) and PhRMA Foundation Fellowship to JMK