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PMID: 8747920 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

New seizure frequency QTL and the complex genetics of epilepsy in EL mice.

Mammalian genome : official journal of the International Mammalian Genome Society ·Vol. 6 ·No. 12 ·1995-12-00 ·Pages 830-8

Frankel WN, Valenzuela A, Lutz CM, Johnson EW, Dietrich WF, Coffin JM

Abstract

EL/Suz (EL) mice experience recurrent seizures that are similar to common partial complex epilepsy in humans. In the mice, seizures occur naturally at 90-100 days of age, but can be induced in younger mice and analyzed as a semi-quantitative trait after gentle rhythmic stimulation. A previous genetic mapping study of EL backcrosses to the strains ABP/LeJ or DBA/2J showed two quantitative trait loci (QTL) with large effects on seizure frequency (El1, Chr 9; El2, Chr 2) and implied the existence of other QTL with lesser effects. To further the understanding of EL-derived seizure alleles, we examined intercross progeny of EL and the strains ABP/LeJ and DDY/Jcl, and also a backcross of (EL x DDY)F1 hybrids to DDY. A new large-effect seizure frequency QTL was found (El5, Chr 14), a more minor QTL confirmed (El3, Chr 10), and two additional QTL proposed (El4, Chr 9; El6, Chr 11). The serotonin receptor gene, Htr2a, maps near and is a candidate for El5, and linkages of other serotonin receptor genes to seizure frequency QTL are noted. In addition, a strong gender effect was revealed, and epistasis was found between Chr 9 and Chr 14 markers. Despite this progress, however, our results revealed a more complex determinism of epilepsy in EL mice than previously described. In particular, no single El locus or pair was essential for frequent seizures, as QTL with large effects, such as El5, El2, and El1, were highly dependent on genetic context. Our studies highlight the importance of gene interaction in some complex mammalian traits defined by natural variation.

MeSH Terms
Animals Base Sequence Crosses, Genetic Epilepsy/genetics Female Humans Male Mice/genetics Molecular Sequence Data Recurrence Seizures/genetics
Authors & Affiliations
6 authors, click to expand affiliations / ORCID
Frankel W N
Jackson Laboratory, Bar Harbor, Maine 04609, USA.
Valenzuela A
Lutz C M
Johnson E W
Dietrich W F
Coffin J M
References (50)
50 references, click to expand
  1. Regional distribution of tyrosine, tryptophan, and their metabolites in the brain of epileptic El mice.
    Neurochem Res. 1992 Jul;17(7):693-8 PMID: 1407265
  2. The stumbler mutation maps to proximal mouse chromosome 2.
    Mamm Genome. 1994 Nov;5(11):659-62 PMID: 7873875
  3. Polygenic control of autoimmune diabetes in nonobese diabetic mice.
    Nat Genet. 1993 Aug;4(4):404-9 PMID: 8401590
  4. A linkage map of endogenous murine leukemia proviruses.
    Genetics. 1990 Feb;124(2):221-36 PMID: 2155154
  5. Mendelian factors underlying quantitative traits in tomato: comparison across species, generations, and environments.
    Genetics. 1991 Jan;127(1):181-97 PMID: 1673106
  6. Prevention of diabetes in the NOD mouse: implications for therapeutic intervention in human disease.
    Immunol Today. 1994 Mar;15(3):115-20 PMID: 8172643
  7. Intracisternal A-type particle elements as genetic markers: detection by repeat element viral element amplified locus-PCR.
    Mamm Genome. 1994 Nov;5(11):688-95 PMID: 7873878
  8. A genetic map of the mouse suitable for typing intraspecific crosses.
    Genetics. 1992 Jun;131(2):423-47 PMID: 1353738
  9. Mapping mendelian factors underlying quantitative traits using RFLP linkage maps.
    Genetics. 1989 Jan;121(1):185-99 PMID: 2563713
  10. Local cerebral glucose utilization in epileptic seizures of the mutant El mouse.
    Brain Res. 1983 May 5;266(2):359-63 PMID: 6871672
  11. Enhanced aspartate release related to epilepsy in (EL) mice.
    J Neurochem. 1994 Aug;63(2):592-5 PMID: 7913488
  12. The GABAergic role of the epileptogenesis in the El mouse.
    Jpn J Psychiatry Neurol. 1989 Sep;43(3):557-8 PMID: 2625798
  13. The MEV mouse linkage testing stock: mapping 30 novel proviral insertions and establishment of an improved stock.
    Genomics. 1993 May;16(2):380-94 PMID: 8390965
  14. Evidence for a multigenic system controlling methyl-beta-carboline-3-carboxylate (beta-CCM)-induced seizures.
    Behav Genet. 1994 May;24(3):285-97 PMID: 7945158
  15. Depth EEG in mutant epileptic E1 mice: demonstration of secondary generalization of the seizure from the hippocampus.
    Electroencephalogr Clin Neurophysiol. 1993 Mar;86(3):205-12 PMID: 7680997
  16. MAPMAKER: an interactive computer package for constructing primary genetic linkage maps of experimental and natural populations.
    Genomics. 1987 Oct;1(2):174-81 PMID: 3692487
  17. Selective DNA pooling for determination of linkage between a molecular marker and a quantitative trait locus.
    Genetics. 1994 Dec;138(4):1365-73 PMID: 7896115
  18. Genetic dissection of complex traits.
    Science. 1994 Sep 30;265(5181):2037-48 PMID: 8091226
  19. Regional excitatory and inhibitory amino acid levels in epileptic El mouse brain.
    Neurochem Res. 1990 Aug;15(8):821-5 PMID: 2215861
  20. Reduced uptake and release of 5-hydroxytryptamine and taurine in the cerebral cortex of epileptic El mice.
    Epilepsy Res. 1987 Jan;1(1):40-5 PMID: 3504382
  21. New strains of seizure-prone mice.
    Brain Res. 1990 Nov 26;534(1-2):94-8 PMID: 2073601
  22. Paroxysmal discharges in the electroencephalogram of the E1 mouse.
    Experientia. 1976 Mar 15;32(3):336-8 PMID: 1253902
  23. Crossbreeding analysis of the mouse epilepsy.
    J UOEH. 1986 Mar 20;8 Suppl:417-24 PMID: 3726316
  24. Seizure patterns and electroencephalograms of E1 mouse.
    Electroencephalogr Clin Neurophysiol. 1977 Sep;43(3):299-311 PMID: 70331
  25. Mouse chromosomes 4 and 13 are involved in beta-carboline-induced seizures.
    J Hered. 1995 Jul-Aug;86(4):274-9 PMID: 7657995
  26. A simple regression method for mapping quantitative trait loci in line crosses using flanking markers.
    Heredity (Edinb). 1992 Oct;69(4):315-24 PMID: 16718932
  27. Multifactorial inheritance of neural tube defects: localization of the major gene and recognition of modifiers in ct mutant mice.
    Nat Genet. 1994 Apr;6(4):357-62 PMID: 8054974
  28. Resolution of quantitative traits into Mendelian factors by using a complete linkage map of restriction fragment length polymorphisms.
    Nature. 1988 Oct 20;335(6192):721-6 PMID: 2902517
  29. Murine serotonin transporter: sequence and localization to chromosome 11.
    Mamm Genome. 1993;4(5):283-4 PMID: 8507984
  30. Congenic strains reveal effects of the epilepsy quantitative trait locus, El2, separate from other El loci.
    Mamm Genome. 1995 Dec;6(12):839-43 PMID: 8747921
  31. A genetic map of the mouse with 4,006 simple sequence length polymorphisms.
    Nat Genet. 1994 Jun;7(2 Spec No):220-45 PMID: 7920646
  32. Brain monoamine levels and E1 mouse convulsions.
    Folia Psychiatr Neurol Jpn. 1981;35(3):261-6 PMID: 6173293
  33. Genetic epilepsy model derived from common inbred mouse strains.
    Genetics. 1994 Oct;138(2):481-9 PMID: 7828829
  34. Epistasis and its contribution to genetic variance components.
    Genetics. 1995 Mar;139(3):1455-61 PMID: 7768453
  35. Epileptic seizure of El mouse initiates at the parietal cortex: depth EEG observation in freely moving condition using buffer amplifier.
    Brain Res. 1993 Apr 9;608(1):52-7 PMID: 8495349
  36. Amino acid metabolism in the brain with convulsive disorders. Part I: Free amino acid patterns in the brain of E1 mouse with convulsive seizure.
    Brain Dev. 1984;6(1):17-21 PMID: 6428249
  37. Genetic identification of Mom-1, a major modifier locus affecting Min-induced intestinal neoplasia in the mouse.
    Cell. 1993 Nov 19;75(4):631-9 PMID: 8242739
  38. Biochemical correlates of epilepsy in the E1 mouse: analysis of glial fibrillary acidic protein and gangliosides.
    J Neurochem. 1992 Feb;58(2):752-60 PMID: 1729417
  39. High levels of quinolinic acid in brain of epilepsy-prone E1 mice.
    Brain Res. 1993 Aug 13;619(1-2):195-8 PMID: 8374778
  40. Eating disorder and epilepsy in mice lacking 5-HT2c serotonin receptors.
    Nature. 1995 Apr 6;374(6522):542-6 PMID: 7700379
  41. Amino acid metabolism in the brain with convulsive disorders. Part 2: The effects of anticonvulsants on convulsions and free amino acid patterns in the brain of El mouse.
    Brain Dev. 1984;6(1):22-6 PMID: 6329016
  42. The serotonin 5-HT1B receptor subtype (Htr1b) gene maps to mouse chromosome 9.
    Mamm Genome. 1993;4(7):397-8 PMID: 8358175
  43. Age- and seizure-related changes in noradrenaline and dopamine in several brain regions of epileptic El mice.
    Neurochem Res. 1993 Feb;18(2):111-7 PMID: 8474554
  44. Glial cell-specific expression of the serotonin 2 receptor gene: selective reactivation of a repressed promoter.
    Brain Res Mol Brain Res. 1993 Nov;20(3):181-91 PMID: 8302156
  45. Increase of brain taurine contents of E1 mice by physiological stimulation.
    Jpn J Pharmacol. 1979 Aug;29(4):503-7 PMID: 537268
  46. Increased plasma glutamic acid in a genetic model of epilepsy.
    Neurochem Res. 1992 Mar;17(3):293-6 PMID: 1352388
  47. Effects of dietary zinc status on seizure susceptibility and hippocampal zinc content in the El (epilepsy) mouse.
    Brain Res. 1990 Oct 8;529(1-2):16-22 PMID: 2282491
  48. Ceruloplasmin gene defect associated with epilepsy in EL mice.
    Nat Genet. 1994 Apr;6(4):426-31 PMID: 7914452
  49. The anticonvulsant effect of citalopram on El mice, and the levels of tryptophan and tyrosine and their metabolites in the brain.
    Neurochem Res. 1994 Apr;19(4):463-7 PMID: 7520538
  50. Genes for epilepsy mapped in the mouse.
    Science. 1991 Aug 9;253(5020):669-73 PMID: 1871601
Article Info
Journal
Mammalian genome : official journal of the International Mammalian Genome Society
Abbr.
Mamm Genome
ISSN
0938-8990
DOI
10.1007/BF00292431
Published
1995-12-00
Pages
830-8
Language
English
Region
United States
NLM ID
9100916
Subset
IM
Grants
NINDS NIH HHS · NS31348 · United States
External Links
PubMed source DOI: 10.1007/BF00292431 View journal details
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