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Electroconvulsive thresholds of inbred mouse strains
W N Frankel1, L Taylor, B Beyer
1The Jackson Laboratory, Bar Harbor, Maine 04609, USA. wnf@jax.org
Abstract:
The electroconvulsive threshold (ECT) test is used commonly in the screening of anti-epileptic drugs in rodent models, but little is known about its genetic or mechanistic basis. Thresholds for minimal clonic, maximal tonic, or psychomotor (partial) seizures were determined in 16 different inbred mouse strains in two different laboratories. A wide range of thresholds was observed, suggesting that a variety of neuroexcitability alleles exist in inbred strains. Although there was generally good cross-strain correlation between the three seizure types, several outlier strains were detected, showing that genetically encoded differences can affect the ability of a particular seizure type to spread through the brain. Furthermore, the relative seizure susceptibility of a strain was comparable between the two laboratories, suggesting that despite different test sites, instrumentation, and personnel, the ECT assay is portable and that common inbred strains can often be relied upon as calibration standards. Last, the ECT paradigm was also sensitive enough to detect single locus differences, laying the groundwork for mutation screens for new neuroexcitability models.
Insights
The electroconvulsive threshold (ECT) test reveals genetic variations in neuroexcitability across mouse strains. This assay is reliable for screening anti-epileptic drugs and identifying genetic differences in seizure susceptibility.
Area of Science:
- Neuroscience
- Genetics
- Pharmacology
Background:
- The electroconvulsive threshold (ECT) test is a standard method for evaluating anti-epileptic drug efficacy in rodent models.
- The genetic underpinnings and mechanistic basis of ECT responses remain largely unexplored.
- Understanding genetic contributions to seizure susceptibility is crucial for developing targeted therapies.
Purpose of the Study:
- To investigate the genetic basis of neuroexcitability using the ECT test across different inbred mouse strains.
- To assess the reliability and portability of the ECT assay across multiple laboratories.
- To determine if the ECT paradigm can detect single-locus genetic differences relevant to seizure disorders.
Main Methods:
- Determined seizure thresholds (clonic, tonic, psychomotor) in 16 inbred mouse strains across two independent laboratories.
- Analyzed the range of thresholds and cross-strain correlations for different seizure types.
- Evaluated the consistency of strain seizure susceptibility between laboratories.
Main Results:
- Observed significant variations in seizure thresholds among mouse strains, indicating diverse neuroexcitability alleles.
- Found generally good correlations between seizure types, with notable exceptions in outlier strains, suggesting specific genetic influences on seizure propagation.
- Demonstrated high comparability of relative seizure susceptibility between laboratories, confirming the ECT assay's portability.
- Confirmed the ECT paradigm's sensitivity in detecting single-locus differences.
Conclusions:
- Inbred mouse strains exhibit substantial genetic variability in neuroexcitability, influencing seizure susceptibility and propagation.
- The ECT test is a robust and portable assay suitable for cross-laboratory comparisons and serves as a reliable calibration standard.
- The ECT assay's sensitivity to single-locus differences provides a foundation for future genetic screens to identify novel neuroexcitability genes and models.