Mapping Loci for Pentylenetetrazol-Induced Seizure Susceptibility in Mice

Abstract

DBA/2J (D2) and C57BL/6J (B6) mice exhibit differential sensitivity to seizures induced by various chemical and physical methods, with D2 mice being relatively sensitive and B6 mice relatively resistant. We conducted studies in mature D2, B6, F1, and F2 intercross mice to investigate behavioral seizure responses to pentylenetetrazol (PTZ) and to map the location of genes that influence this trait. Mice were injected with PTZ and observed for 45 min. Seizure parameters included latencies to focal clonus, generalized clonus, and maximal seizure. Latencies were used to calculate a seizure score that was used for quantitative mapping. F2 mice (n = 511) exhibited a wide range of latencies with two-thirds of the group expressing maximal seizure. Complementary statistical analyses identified loci on proximal (near D1Mit11) and distal chromosome 1 (near D1Mit17) as having the strongest and most significant effects in this model. Another locus of significant effect was detected on chromosome 5 (near D5Mit398). Suggestive evidence for additional PTZ seizure-related loci was detected on chromosomes 3, 4, and 6. Of the seizure-related loci identified in this study, those on chromosomes 1 (distal), 4, and 5 map close to loci previously identified in a similar F2 population tested with kainic acid. Results document that the complex genetic influences controlling seizure response in B6 and D2 mice are partially independent of the nature of the chemoconvulsant stimulus with a locus on distal chromosome 1 being of fundamental importance.

Parvalbumin deficiency affects network properties resulting in increased susceptibility to epileptic seizures

“…The seizure intensity was recorded using the following scale: (1) decreased locomotor activity; (2) twitching either of the whole body or localized; (3) 1 -20 myoclonic body jerks during the 10-min period; (4) more than 20 myoclonic body jerks during the 10-min period; (5) clonic forelimb convulsions; (6) generalized tonic -clonic seizures, characterized by forelimb and/or hindlimb clonus and tonus resulting in episodes of falling down; (7) status epilepticus (SE); (8) death. Similar scaling of PTZ-induced seizure intensities in mice has been reported before (Ferraro et al, 1999). Animals were observed during a 20-min period.…”

Minozac Treatment Prevents Increased Seizure Susceptibility in a Mouse “Two-Hit” Model of Closed Skull Traumatic Brain Injury and Electroconvulsive Shock-Induced Seizures

“…Subtle clinical signs of seizures including facial movement and forelimb clonus could not be reliably detected in this strain and were therefore excluded to minimize subjectivity in seizure assessment (Hunt et al, 2009). We defined seizure onset as forelimb clonus based on previously published methods (Ferraro et al, 1999;Frankel et al, 2001). We defined three responses on the continuum of the effects of ECS.…”

Genetic Markers of a Munc13 Protein Family Member, BAIAP3, Are Gender Specifically Associated with Anxiety and Benzodiazepine Abuse in Mice and Humans

“…Seizure activity was induced in wakeful mice by using a single IP injection of PTZ (50 mg/kg body weight) (33). After injection of the compound, the mouse was placed in a small, clear home cage and closely observed for 30 min.…”

“…The weighting factors (0.2, 0.3 and 0.5) in the equation were included as a means of incorporating a measure of the progressive nature of the PTZ-induced seizure phenotype into the severity rating because generalized clonus is regarded as a more significant event than partial clonus and tonic hind limb extension as the most severe component of the phenotype. Therefore, the seizure score reflects the degree of progression of the seizure phenotype in each mouse (33 Midazolam oral self-administration and behavior testing in the addicted state. To induce benzodiazepine dependence as a prerequisite for oral selfadministration (document of addiction), group-housed mice received midazolam (ratiopharm) in 2% sucrose (to reduce the bitter taste), instead of drinking water.…”