Electroconvulsive seizure thresholds and kindling acquisition rates are altered in mouse models of humanKCNQ2andKCNQ3mutations for benign familial neonatal convulsions
| Autor: | Chris Pappas, Mark Leppert, Timothy H. Pruess, E. Jill Dahle, Nanda A. Singh, H. Steve White, Karen S. Wilcox, James F. Otto |
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| Rok vydání: | 2009 |
| Předmět: |
Male
Heterozygote medicine.medical_specialty Mutation Missense Action Potentials Nerve Tissue Proteins Hindlimb Neurological disorder KCNQ3 Potassium Channel Central nervous system disease Electrocardiography Mice Epilepsy Sex Factors Seizures Internal medicine Convulsion Kindling Neurologic medicine Animals Humans KCNQ2 Potassium Channel Genetic Predisposition to Disease Gene Knock-In Techniques Seizure threshold Kindling Heterozygote advantage medicine.disease Electric Stimulation Epilepsy Benign Neonatal Disease Models Animal Endocrinology Neurology Mutation Female Neurology (clinical) medicine.symptom Psychology Neuroscience |
| Zdroj: | Epilepsia. 50:1752-1759 |
| ISSN: | 1528-1167 0013-9580 |
| DOI: | 10.1111/j.1528-1167.2009.02100.x |
| Popis: | Summary Purpose: Benign familial neonatal convulsions (BFNC) is caused by mutations in the KCNQ2 and KCNQ3 genes, which encode subunits of the M-type potassium channel. The purpose of this study was to examine the effects of orthologous BFNC-causing mutations on seizure thresholds and the acquisition of corneal kindling in mice with heterozygous expression of the mutations. Methods: The effects of the Kcnq2 gene A306T mutation and the Kcnq3 gene G311V mutation were determined for minimal clonic, minimal tonic hindlimb extension, and partial psychomotor seizures. The rate of corneal kindling acquisition was also determined for Kcnq2 A306T and Kcnq3 G311V mice. Results: Seizure thresholds were significantly altered relative to wild-type animals in the minimal clonic, minimal tonic hindlimb extension, and partial psychomotor seizure models. Differences in seizure threshold were found to be dependent on the mutation expressed, the seizure testing paradigm, the genetic background strain, and the gender of the animal. Mutations in Kcnq2 and Kcnq3 were associated with an increased rate of corneal kindling. In the Kcnq2 A306T mice, an increased incidence of death occurred during and immediately following the conclusion of the kindling acquisition period. Conclusions: These results suggest that genetic alterations in the subunits that underlie the M-current and cause BFNC alter seizure susceptibility in a sex-, mouse strain-, and seizure-test dependent manner. Although the heterozygous mice do not appear to have spontaneous seizures, the increased seizure susceptibility and incidence of death during and after kindling suggests that these mutations lead to altered excitability in these animals. |
| Databáze: | OpenAIRE |
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