title: Analysis of a quantitative trait locus for seizure susceptibility in mice using bacterial artificial chromosome-mediated gene transfer.
abstract: OBJECTIVE
  Previous quantitative trait loci (QTL) mapping studies from our laboratory identified a 6.6 Mb segment of distal chromosome 1 that contains a gene (or genes) having a strong influence on the difference in seizure susceptibility between C57BL/6 (B6) and DBA/2 (D2) mice. A gene transfer strategy involving a bacterial artificial chromosome (BAC) DNA construct that contains several candidate genes from the critical interval was used to test the hypothesis that a strain-specific variation in one (or more) of the genes is responsible for the QTL effect.
  
  
  METHODS
  Fertilized oocytes from a seizure-sensitive congenic strain (B6.D2-Mtv7a/Ty-27d) were injected with BAC DNA and three independent founder lines of BAC-transgenic mice were generated. Seizure susceptibility was quantified by measuring maximal electroshock seizure threshold (MEST) in transgenic mice and nontransgenic littermates.
  
  
  RESULTS
  Seizure testing documented significant MEST elevation in all three transgenic lines compared to littermate controls. Allele-specific RT-PCR analysis confirmed gene transcription from genome-integrated BAC DNA and copy-number-dependent phenotypic effects were observed.
  
  
  CONCLUSIONS
  Results of this study suggest that the gene(s) responsible for the major chromosome 1 seizure QTL is found on BAC RPCI23-157J4 and demonstrate the utility of in vivo gene transfer for studying quantitative trait genes in mice. Further characterization of this transgenic model will provide new insight into mechanisms of seizure susceptibility.
authors.affiliation: Center for Neurobiology and Behavior, Department of Psychiatry, University of Pennsylvania, Philadelphia, PennsylvaniaResearch Service, Veteran's Affairs Medical Center, Coatesville, PennsylvaniaDepartment of Neurology, University of Cincinnati, Cincinnati, Ohio, U.S.A.
authors.forename: Thomas N
authors.initials: TN
authors.lastname: Ferraro
authors.affiliation: Center for Neurobiology and Behavior, Department of Psychiatry, University of Pennsylvania, Philadelphia, PennsylvaniaResearch Service, Veteran's Affairs Medical Center, Coatesville, PennsylvaniaDepartment of Neurology, University of Cincinnati, Cincinnati, Ohio, U.S.A.
authors.forename: Gregory T
authors.initials: GT
authors.lastname: Golden
authors.affiliation: Center for Neurobiology and Behavior, Department of Psychiatry, University of Pennsylvania, Philadelphia, PennsylvaniaResearch Service, Veteran's Affairs Medical Center, Coatesville, PennsylvaniaDepartment of Neurology, University of Cincinnati, Cincinnati, Ohio, U.S.A.
authors.forename: John P
authors.initials: JP
authors.lastname: Dahl
authors.affiliation: Center for Neurobiology and Behavior, Department of Psychiatry, University of Pennsylvania, Philadelphia, PennsylvaniaResearch Service, Veteran's Affairs Medical Center, Coatesville, PennsylvaniaDepartment of Neurology, University of Cincinnati, Cincinnati, Ohio, U.S.A.
authors.forename: George G
authors.initials: GG
authors.lastname: Smith
authors.affiliation: Center for Neurobiology and Behavior, Department of Psychiatry, University of Pennsylvania, Philadelphia, PennsylvaniaResearch Service, Veteran's Affairs Medical Center, Coatesville, PennsylvaniaDepartment of Neurology, University of Cincinnati, Cincinnati, Ohio, U.S.A.
authors.forename: Candice L
authors.initials: CL
authors.lastname: Schwebel
authors.affiliation: Center for Neurobiology and Behavior, Department of Psychiatry, University of Pennsylvania, Philadelphia, PennsylvaniaResearch Service, Veteran's Affairs Medical Center, Coatesville, PennsylvaniaDepartment of Neurology, University of Cincinnati, Cincinnati, Ohio, U.S.A.
authors.forename: Ross
authors.initials: R
authors.lastname: MacDonald
authors.affiliation: Center for Neurobiology and Behavior, Department of Psychiatry, University of Pennsylvania, Philadelphia, PennsylvaniaResearch Service, Veteran's Affairs Medical Center, Coatesville, PennsylvaniaDepartment of Neurology, University of Cincinnati, Cincinnati, Ohio, U.S.A.
authors.forename: Falk W
authors.initials: FW
authors.lastname: Lohoff
authors.affiliation: Center for Neurobiology and Behavior, Department of Psychiatry, University of Pennsylvania, Philadelphia, PennsylvaniaResearch Service, Veteran's Affairs Medical Center, Coatesville, PennsylvaniaDepartment of Neurology, University of Cincinnati, Cincinnati, Ohio, U.S.A.
authors.forename: Wade H
authors.initials: WH
authors.lastname: Berrettini
authors.affiliation: Center for Neurobiology and Behavior, Department of Psychiatry, University of Pennsylvania, Philadelphia, PennsylvaniaResearch Service, Veteran's Affairs Medical Center, Coatesville, PennsylvaniaDepartment of Neurology, University of Cincinnati, Cincinnati, Ohio, U.S.A.
authors.forename: Russell J
authors.initials: RJ
authors.lastname: Buono
mesh_terms: D000818:Animals; D015153:Blotting, Western; D001921:Brain / Q000378:metabolism; D002874:Chromosome Mapping; D022202:Chromosomes, Artificial, Bacterial / Q000235:genetics*; D004195:Disease Models, Animal; D004597:Electroshock; D005260:Female; D005786:Gene Expression Regulation; D018014:Gene Transfer Techniques; D020022:Genetic Predisposition to Disease / Q000235:genetics; D008297:Male; D051379:Mice; D020297:Mice, Congenic; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D008957:Models, Genetic; D040641:Quantitative Trait Loci / Q000235:genetics*; D012640:Seizures / Q000235:genetics* / Q000378:metabolism