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beta-Carboline-induced seizures in mice: genetic analysis
C Desforges1, P Venault, R H Dodd
1URA 1294, CNRS, UFR Biomédicale Paris V, France.
Pharmacology, Biochemistry, and Behavior
|December 1, 1989
Summary
Inbred mouse strains BALB/cBy and C57BL/6By show different susceptibility to methyl beta-carboline-3-carboxylate (beta-CCM) induced seizures. Genetic analysis suggests a complex inheritance pattern for this seizure susceptibility.
Area of Science:
- Neuroscience
- Genetics
- Pharmacology
Background:
- Benzodiazepine inverse agonists, such as methyl beta-carboline-3-carboxylate (beta-CCM), are known to induce seizures.
- Inbred mouse strains exhibit varying responses to pharmacological challenges, indicating genetic influences on behavior and physiology.
Purpose of the Study:
- To investigate the genetic basis of differential susceptibility to beta-CCM-induced seizures between BALB/cBy and C57BL/6By mouse strains.
- To determine if maternal environmental or heterosomal factors contribute to the observed strain differences.
Main Methods:
- Administered beta-CCM (5 mg/kg) to BALB/cBy and C57BL/6By mice and recorded seizure incidence.
- Conducted reciprocal F1 crosses to assess maternal and heterosomal effects.
- Utilized recombinant inbred strains (RIS) for genetic segregation analysis.
Main Results:
- BALB/cBy mice (74%) were significantly more susceptible to beta-CCM-induced seizures than C57BL/6By mice (13%).
- No sex differences in seizure susceptibility were observed.
- Analysis of F1 hybrids did not reveal significant maternal environmental or heterosomal influences.
- Recombinant inbred strain analysis indicated a two-group partition and suggested that while a single gene segregation model could not be rejected, evidence partially weakened this hypothesis.
Conclusions:
- Significant genetic differences underlie the susceptibility to beta-CCM-induced seizures between BALB/cBy and C57BL/6By mice.
- The inheritance pattern of beta-CCM-induced seizure susceptibility appears complex, potentially involving more than one genetic locus or interaction.