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Epilepsy-associated gene Nedd4-2 mediates neuronal activity and seizure susceptibility through AMPA receptors

Fig 4

Genetically reducing GluA1 normalizes elevated seizure susceptibility in Nedd4-2andi mice.

(A) Western blots of GluA1, Nedd4-2, and Gapdh from 3 representative mice of each of the 4 genotypes: Nedd4-2wt/wt GluA1+/+, Nedd4-2wt/wt GluA1+/-, Nedd4-2andi/andi GluA1+/+, and Nedd4-2andi/andi GluA1+/-. Quantification of GluA1 is shown on the right (Six mice of each genotype were obtained for quantification. ANOVA with post-hoc Tukey test, **p < 0.01). (B) Four-week old mice with each of the 4 genotypes mentioned in (A) were intraperitoneally injected with kainic acid (15, 30, or 60 mg/kg). The number of mice used in each condition is shown on the top of each bar. Mice showing stage 4 and/or 5 seizure activity are counted as 1 while mice showing stage 3 seizure or under are counted as 0. The statistical results after a 2-way ANOVA with post-hoc Tukey test are as below: Nedd4-2wt/wt GluA1+/+ vs Nedd4-2andi/andi GluA1+/+, *p < 0.05; Nedd4-2andi/andi GluA1+/+ vs Nedd4-2andi/andi GluA1+/-, *p < 0.05; Nedd4-2wt/wt GluA1+/+ vs Nedd4-2wt/wt GluA1+/-, p > 0.05; Nedd4-2wt/wt GluA1+/+ vs Nedd4-2andi/andi GluA1+/-, *p > 0.05.

Fig 4

doi: https://doi.org/10.1371/journal.pgen.1006634.g004