title: Use of chromosome substitution strains to identify seizure susceptibility loci in mice.
abstract: Seizure susceptibility varies among inbred mouse strains. Chromosome substitution strains (CSS), in which a single chromosome from one inbred strain (donor) has been transferred onto a second strain (host) by repeated backcrossing, may be used to identify quantitative trait loci (QTLs) that contribute to seizure susceptibility. QTLs for susceptibility to pilocarpine-induced seizures, a model of temporal lobe epilepsy, have not been reported, and CSS have not previously been used to localize seizure susceptibility genes. We report QTLs identified using a B6 (host) x A/J (donor) CSS panel to localize genes involved in susceptibility to pilocarpine-induced seizures. Three hundred fifty-five adult male CSS mice, 58 B6, and 39 A/J were tested for susceptibility to pilocarpine-induced seizures. Highest stage reached and latency to each stage were recorded for all mice. B6 mice were resistant to seizures and slower to reach stages compared to A/J mice. The CSS for Chromosomes 10 and 18 progressed to the most severe stages, diverging dramatically from the B6 phenotype. Latencies to stages were also significantly shorter for CSS10 and CSS18 mice. CSS mapping suggests seizure susceptibility loci on mouse Chromosomes 10 and 18. This approach provides a framework for identifying potentially novel homologous candidate genes for human temporal lobe epilepsy.
authors.affiliation: Department of Neurology, Columbia University, New York, NY 10032, USA. mw211@columbia.edu
authors.forename: Melodie R
authors.initials: MR
authors.lastname: Winawer
authors.forename: Rachel
authors.initials: R
authors.lastname: Kuperman
authors.forename: Martin
authors.initials: M
authors.lastname: Niethammer
authors.forename: Steven
authors.initials: S
authors.lastname: Sherman
authors.forename: Daniel
authors.initials: D
authors.lastname: Rabinowitz
authors.forename: Irene Plana
authors.initials: IP
authors.lastname: Guell
authors.forename: Christine A
authors.initials: CA
authors.lastname: Ponder
authors.forename: Abraham A
authors.initials: AA
authors.lastname: Palmer
mesh_terms: D000818:Animals; D002875:Chromosomes / Q000235:genetics; D020022:Genetic Predisposition to Disease; D005821:Genetic Techniques; D008297:Male; D051379:Mice; D008805:Mice, Inbred A; D008815:Mice, Inbred Strains; D010862:Pilocarpine / Q000633:toxicity; D040641:Quantitative Trait Loci; D012640:Seizures / Q000139:chemically induced / Q000235:genetics*; D013045:Species Specificity
chemical_list: D010862:Pilocarpine