Mapping murine loci for seizure response to kainic acid |
| |
| Authors: | T. N. Ferraro G. T. Golden G. G. Smith N. J. Schork P. St. Jean C. Ballas H. Choi W. H. Berrettini |
| |
| Affiliation: | (1) Department of Psychiatry, Thomas Jefferson University, Philadelphia, Pennsylvania 19107, USA, US;(2) Department of Pharmacology, Thomas Jefferson University, Philadelphia, Pennsylvania 19107, USA, US;(3) Department of Neurology, Thomas Jefferson University, Philadelphia, Pennsylvania 19107, USA, US;(4) Research Service, Department of Veterans Affairs Medical Center, Coatesville, Pennsylvania, 19320, USA, US;(5) Departments of Epidemiology and Biostatistics, Case Western Reserve University, Cleveland, Ohio 44106, USA, US;(6) Department of Genetics, Case Western Reserve University, Cleveland, Ohio 44106, USA, US;(7) Department of Biostatistics, Harvard University, Boston, Massachusetts, USA, US;(8) The Jackson Laboratory, Bar Harbor, Maine 04609, USA, US |
| |
| Abstract: | Mature DBA/2J (D2) mice are very sensitive to seizures induced by various chemical and physical stimuli, whereas C57BL/6J (B6) mice are relatively seizure resistant. We have conducted a genome-wide search for quantitative trait loci (QTLs) influencing the differential sensitivity of these strains to kainic acid (KA)-induced seizures by studying an F2 intercross population. Parental, F1, and F2 mice (8–10 weeks of age) were injected subcutaneously with 25 mg/kg of KA and observed for 3 h. Latencies to focal and generalized seizures and status epilepticus were recorded and used to calculate an overall seizure score. Results of seizure testing indicated that the difference in susceptibility to KA-induced seizures between D2 and B6 mice is a polygenic phenomenon with at least 65% of the variance due to genetic factors. First-pass genome screening (10-cM marker intervals) in F2 progeny (n = 257) documented a QTL of moderate effect on Chromosome (Chr) 1 with a peak LOD score of 5.5 (17% of genetic variance explained) localized between D1Mit30 and D1Mit16. Provisional QTLs of small effect were detected on Chr 11 (D11Mit224–D11Mit14), 15 (D15Mit6–D15Mit46) and 18 (D18Mit9–D18Mit144). Multiple locus models generally confirmed the Mapmaker/QTL results and also provided evidence for another QTL on Chr 4 (D4Mit9). Multilocus analysis of seizure severity suggested that additional loci on Chrs 5 (D5Mit11), 7 (D7Mit66), and 15 (D15Nds2) might also contribute to KA-induced seizure response. Overall, our results document a complex genetic determinism for KA-induced seizures in these mouse strains with contributions from as many as eight QTLs. Received: 16 April 1996 / Accepted: 21 October 1996 |
| |
| Keywords: | |
| 本文献已被 SpringerLink 等数据库收录！ |
|
