Home LiteratureArticle Details
PMID: 17242861 Published · ppublish English Journal Article Research Support, N.I.H., Extramural

Use of chromosome substitution strains to identify seizure susceptibility loci in mice.

Mammalian genome : official journal of the International Mammalian Genome Society ·Vol. 18 ·No. 1 ·2007-01-00 ·Pages 23-31

Winawer MR, Kuperman R, Niethammer M, Sherman S, Rabinowitz D, Guell IP, Ponder CA, Palmer AA

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.

MeSH Terms
Animals Chromosomes/genetics Genetic Predisposition to Disease Genetic Techniques Male Mice Mice, Inbred A Mice, Inbred Strains Pilocarpine/toxicity Quantitative Trait Loci Seizures/chemically induced,genetics Species Specificity
Chemicals
Pilocarpine
Authors & Affiliations
8 authors, click to expand affiliations / ORCID
Winawer Melodie R
Department of Neurology, Columbia University, New York, NY 10032, USA. [email protected]
Kuperman Rachel
Niethammer Martin
Sherman Steven
Rabinowitz Daniel
Guell Irene Plana
Ponder Christine A
Palmer Abraham A
References (66)
66 references, click to expand
  1. The biology of epilepsy genes.
    Annu Rev Neurosci. 2003;26:599-625 PMID: 14527270
  2. Mouse strain differences in kainic acid sensitivity, seizure behavior, mortality, and hippocampal pathology.
    Neuroscience. 2003;122(2):551-61 PMID: 14614919
  3. Chromosome substitution strains: some quantitative considerations for genome scans and fine mapping.
    Mamm Genome. 2003 Nov;14(11):723-32 PMID: 14722722
  4. Genetic dissection of complex traits with chromosome substitution strains of mice.
    Science. 2004 Apr 16;304(5669):445-8 PMID: 15031436
  5. Fine mapping of a seizure susceptibility locus on mouse Chromosome 1: nomination of Kcnj10 as a causative gene.
    Mamm Genome. 2004 Apr;15(4):239-51 PMID: 15112102
  6. Association between variation in the human KCNJ10 potassium ion channel gene and seizure susceptibility.
    Epilepsy Res. 2004 Feb;58(2-3):175-83 PMID: 15120748
  7. Genetic control of sensitivity to hippocampal cell death induced by kainic acid: a quantitative trait loci analysis.
    J Comp Neurol. 2004 Sep 6;477(1):96-107 PMID: 15281082
  8. Mutations in EFHC1 cause juvenile myoclonic epilepsy.
    Nat Genet. 2004 Aug;36(8):842-9 PMID: 15258581
  9. Modification of seizure activity by electrical stimulation. II. Motor seizure.
    Electroencephalogr Clin Neurophysiol. 1972 Mar;32(3):281-94 PMID: 4110397
  10. Review: cholinergic mechanisms and epileptogenesis. The seizures induced by pilocarpine: a novel experimental model of intractable epilepsy.
    Synapse. 1989;3(2):154-71 PMID: 2648633
  11. Genetic dissection of susceptibility to audiogenic seizures in inbred mice.
    Proc Natl Acad Sci U S A. 1991 Jun 15;88(12):5408-12 PMID: 2052619
  12. Confirmation of the influence of a chromosome 7 locus on susceptibility to audiogenic seizures.
    Mamm Genome. 1992;3(5):250-3 PMID: 1638084
  13. Differential susceptibility to seizures induced by systemic kainic acid treatment in mature DBA/2J and C57BL/6J mice.
    Epilepsia. 1995 Mar;36(3):301-7 PMID: 7614915
  14. Mouse chromosomes 4 and 13 are involved in beta-carboline-induced seizures.
    J Hered. 1995 Jul-Aug;86(4):274-9 PMID: 7657995
  15. A missense mutation in the neuronal nicotinic acetylcholine receptor alpha 4 subunit is associated with autosomal dominant nocturnal frontal lobe epilepsy.
    Nat Genet. 1995 Oct;11(2):201-3 PMID: 7550350
  16. Mouse chromosome 9 involvement in beta-CCM-induced seizures.
    Neuroreport. 1996 Sep 2;7(13):2226-30 PMID: 8930994
  17. Mapping murine loci for seizure response to kainic acid.
    Mamm Genome. 1997 Mar;8(3):200-8 PMID: 9069121
  18. Genetic determinants of susceptibility to excitotoxic cell death: implications for gene targeting approaches.
    Proc Natl Acad Sci U S A. 1997 Apr 15;94(8):4103-8 PMID: 9108112
  19. Quantitative trait loci involved in genetic predisposition to acute alcohol withdrawal in mice.
    J Neurosci. 1997 May 15;17(10):3946-55 PMID: 9133412
  20. A novel potassium channel gene, KCNQ2, is mutated in an inherited epilepsy of newborns.
    Nat Genet. 1998 Jan;18(1):25-9 PMID: 9425895
  21. A pore mutation in a novel KQT-like potassium channel gene in an idiopathic epilepsy family.
    Nat Genet. 1998 Jan;18(1):53-5 PMID: 9425900
  22. Febrile seizures and generalized epilepsy associated with a mutation in the Na+-channel beta1 subunit gene SCN1B.
    Nat Genet. 1998 Aug;19(4):366-70 PMID: 9697698
  23. Is the underlying cause of epilepsy a major prognostic factor for recurrence?
    Neurology. 1998 Nov;51(5):1256-62 PMID: 9818842
  24. Genetic influences on electrical seizure threshold.
    Brain Res. 1998 Nov 30;813(1):207-10 PMID: 9824700
  25. Mapping quantitative trait loci for seizure response to a GABAA receptor inverse agonist in mice.
    J Neurosci. 1999 May 15;19(10):3731-8 PMID: 10234005
  26. Quantitative trait loci affecting risk for pentobarbital withdrawal map near alcohol withdrawal loci on mouse chromosomes 1, 4, and 11.
    Mamm Genome. 1999 May;10(5):431-7 PMID: 10337613
  27. Mapping loci for pentylenetetrazol-induced seizure susceptibility in mice.
    J Neurosci. 1999 Aug 15;19(16):6733-9 PMID: 10436030
  28. Susceptibility to testicular germ-cell tumours in a 129.MOLF-Chr 19 chromosome substitution strain.
    Nat Genet. 1999 Oct;23(2):237-40 PMID: 10508525
  29. Expression analysis of metabotropic glutamate receptors I and III in mouse strains with different susceptibility to experimental temporal lobe epilepsy.
    Neurosci Lett. 2005 Mar 3;375(3):192-7 PMID: 15694259
  30. Supportive evidence for an allelic association of the human KCNJ10 potassium channel gene with idiopathic generalized epilepsy.
    Epilepsy Res. 2005 Feb;63(2-3):113-8 PMID: 15725393
  31. Genetic modifiers affecting severity of epilepsy caused by mutation of sodium channel Scn2a.
    Mamm Genome. 2005 Sep;16(9):683-90 PMID: 16245025
  32. Chromosomal substitution-dependent differences in cardiovascular responses to sodium pentobarbital.
    Anesth Analg. 2006 Mar;102(3):799-805 PMID: 16492831
  33. Analysing complex genetic traits with chromosome substitution strains.
    Nat Genet. 2000 Mar;24(3):221-5 PMID: 10700173
  34. Cocaine-induced seizure thresholds: quantitative trait loci detection and mapping in two populations derived from the C57BL/6 and DBA/2 mouse strains.
    J Pharmacol Exp Ther. 2000 Apr;293(1):180-7 PMID: 10734168
  35. Mutations of SCN1A, encoding a neuronal sodium channel, in two families with GEFS+2.
    Nat Genet. 2000 Apr;24(4):343-5 PMID: 10742094
  36. Pilocarpine-induced seizures in rodents--17 years on.
    Pol J Pharmacol. 2000 Jan-Feb;52(1):63-5 PMID: 10949124
  37. The nicotinic receptor beta 2 subunit is mutant in nocturnal frontal lobe epilepsy.
    Nat Genet. 2000 Nov;26(3):275-6 PMID: 11062464
  38. Genetic factors in addiction: QTL mapping and candidate gene studies implicate GABAergic genes in alcohol and barbiturate withdrawal in mice.
    Addiction. 2001 Jan;96(1):139-49 PMID: 11177525
  39. Neuronal sodium-channel alpha1-subunit mutations in generalized epilepsy with febrile seizures plus.
    Am J Hum Genet. 2001 Apr;68(4):859-65 PMID: 11254444
  40. Brown Norway chromosome 13 confers protection from high salt to consomic Dahl S rat.
    Hypertension. 2001 Feb;37(2 Pt 2):456-61 PMID: 11230318
  41. First genetic evidence of GABA(A) receptor dysfunction in epilepsy: a mutation in the gamma2-subunit gene.
    Nat Genet. 2001 May;28(1):46-8 PMID: 11326274
  42. Mutant GABA(A) receptor gamma2-subunit in childhood absence epilepsy and febrile seizures.
    Nat Genet. 2001 May;28(1):49-52 PMID: 11326275
  43. A missense mutation of the Na+ channel alpha II subunit gene Na(v)1.2 in a patient with febrile and afebrile seizures causes channel dysfunction.
    Proc Natl Acad Sci U S A. 2001 May 22;98(11):6384-9 PMID: 11371648
  44. A proposed diagnostic scheme for people with epileptic seizures and with epilepsy: report of the ILAE Task Force on Classification and Terminology.
    Epilepsia. 2001 Jun;42(6):796-803 PMID: 11422340
  45. Does the cause of localisation-related epilepsy influence the response to antiepileptic drug treatment?
    Epilepsia. 2001 Mar;42(3):357-62 PMID: 11442153
  46. More evidence for seizure-induced neuron loss: is hippocampal sclerosis both cause and effect of epilepsy?
    Neurology. 2001 Jul 24;57(2):169-70 PMID: 11468296
  47. Volumetric MRI, pathological, and neuropsychological progression in hippocampal sclerosis.
    Neurology. 2001 Jul 24;57(2):184-8 PMID: 11468300
  48. Quantitative genetic study of maximal electroshock seizure threshold in mice: evidence for a major seizure susceptibility locus on distal chromosome 1.
    Genomics. 2001 Jul;75(1-3):35-42 PMID: 11472065
  49. Nav1.1 mutations cause febrile seizures associated with afebrile partial seizures.
    Neurology. 2001 Aug 28;57(4):703-5 PMID: 11524484
  50. Truncation of the GABA(A)-receptor gamma2 subunit in a family with generalized epilepsy with febrile seizures plus.
    Am J Hum Genet. 2002 Feb;70(2):530-6 PMID: 11748509
  51. Renal medullary genes in salt-sensitive hypertension: a chromosomal substitution and cDNA microarray study.
    Physiol Genomics. 2002 Feb 28;8(2):139-49 PMID: 11875192
  52. Mutations in LGI1 cause autosomal-dominant partial epilepsy with auditory features.
    Nat Genet. 2002 Mar;30(3):335-41 PMID: 11810107
  53. Mutations in the LGI1/Epitempin gene on 10q24 cause autosomal dominant lateral temporal epilepsy.
    Hum Mol Genet. 2002 May 1;11(9):1119-28 PMID: 11978770
  54. Congenic mapping of alcohol and pentobarbital withdrawal liability loci to a <1 centimorgan interval of murine chromosome 4: identification of Mpdz as a candidate gene.
    J Neurosci. 2002 May 1;22(9):3730-8 PMID: 11978849
  55. Mutation of GABRA1 in an autosomal dominant form of juvenile myoclonic epilepsy.
    Nat Genet. 2002 Jun;31(2):184-9 PMID: 11992121
  56. A splice-site mutation in GABRG2 associated with childhood absence epilepsy and febrile convulsions.
    Arch Neurol. 2002 Jul;59(7):1137-41 PMID: 12117362
  57. Does convulsive status epilepticus (SE) result in cerebral damage or affect the course of epilepsy--the epidemiological and clinical evidence?
    Prog Brain Res. 2002;135:85-93 PMID: 12143372
  58. New insights from the use of pilocarpine and kainate models.
    Epilepsy Res. 2002 Jun;50(1-2):93-103 PMID: 12151121
  59. Sodium-channel defects in benign familial neonatal-infantile seizures.
    Lancet. 2002 Sep 14;360(9336):851-2 PMID: 12243921
  60. Modulation of cell death by mouse genotype: differential vulnerability to excitatory amino acid-induced lesions.
    Exp Neurol. 2002 Dec;178(2):219-35 PMID: 12504881
  61. Testicular cancer susceptibility in the 129.MOLF-Chr19 mouse strain: additive effects, gene interactions and epigenetic modifications.
    Hum Mol Genet. 2003 Feb 15;12(4):389-98 PMID: 12566386
  62. Mutations in CLCN2 encoding a voltage-gated chloride channel are associated with idiopathic generalized epilepsies.
    Nat Genet. 2003 Apr;33(4):527-32 PMID: 12612585
  63. Neuronal and glial pathological changes during epileptogenesis in the mouse pilocarpine model.
    Exp Neurol. 2003 Jul;182(1):21-34 PMID: 12821374
  64. Is epilepsy a progressive disorder? Prospects for new therapeutic approaches in temporal-lobe epilepsy.
    Lancet Neurol. 2002 Jul;1(3):173-81 PMID: 12849486
  65. Harnessing the mouse to unravel the genetics of human disease.
    Genes Brain Behav. 2002 Jan;1(1):14-26 PMID: 12886946
  66. Sodium channel alpha1-subunit mutations in severe myoclonic epilepsy of infancy and infantile spasms.
    Neurology. 2003 Sep 23;61(6):765-9 PMID: 14504318
Article Info
Journal
Mammalian genome : official journal of the International Mammalian Genome Society
Abbr.
Mamm Genome
ISSN
0938-8990
DOI
10.1007/s00335-006-0087-6
Email
[email protected]
Published
2007-01-00
Epub
2007-00-22
Pages
23-31
Language
English
Region
United States
NLM ID
9100916
PMCID
PMC2640942
Subset
IM
Grants
NIMH NIH HHS · K01 MH070933 · United States
NINDS NIH HHS · K02 NS050429 · United States
NINDS NIH HHS · K02 NS050429-02 · United States
NIMH NIH HHS · MH70933 · United States
External Links
PubMed source DOI: 10.1007/s00335-006-0087-6 PMC Full Text View journal details
Analysis Services
Analysis Services

Contact

No. 2 Wenbo Road, Zhangqiu District, Jinan, Shandong

Qilu Normal University · Genelibs Bioinformatics Lab

750 Shunhua Rd, Jinan

2F, Bldg F, University Science Park

Tel: 0531-88819269

WeChat Official Account

Follow our WeChat subscription account for real-time updates and the latest in medical and biological research.


Business Email

E-mail: [email protected]

Copyright © 2026.Genelibs Jinan Honghui Biotechnology Co., Ltd. 鲁ICP备20007159号-2