Establishment of an epileptic model of pilocarpine in Nedl1 knockout mice

Objective To explore the relationship between Nedl1 gene and epilepsy by constructing a pilocarpine epilepsy model in Nedl1 （nedd4-like ubiquitin protein ligase-1） knockout mice (Nedl1^-/-). Methods C57BL/6 mice were selected to construct Nedl1^-/-mice by the Cre-Loxp system.Wild-type mice (Nedl1^+/+) and Nedl1^-/-mice of the same age were selected to induce epileptic seizures by intraperitoneal injection of pilocarpine.The seizures of the two groups were counted,and the hippocampal Nissl staining and neuropeptide Y （NPY） staining of two groups were compared before and after establishing the epilepsy model. Results Compared to Nedl1^+/+ mice,the seizures in Nedl1^-/-mice were milder （P=00.000）,less frequent （P=00.004）,and the severe seizures （Racine scale score>3） occurred later （P=00.016）.All Nedl1^-/-mice survived,while the mortality rate of Nedl1^+/+ mice was 46.4%.One month after the establishement of epilepsy model,the Nissl staining showed that the number of cells in the hippocampal CA1 region of Nedl1^+/+ mice significantly decreased,and those in the DG region were disordered and consolidated.Nedl1^-/-mice hippocampal Nissl staining showed no significant changes.The immunofluorescence staining of NPY showed that the mossy fiber sprouting in Nedl1^+/+ mice was more obvious than in Nedl1^-/-mice. Conclusion The severity and mortality of seizures in Nedl1^-/-mice are significantly lower than those in Nedl1^+/+ mice.One month after the establishement of epilepsy model,neuronal damage and mossy fiber sprouting in the hippocampus of Nedl1^-/-mice are milder than those in Nedl1^+/+ mice.