A locus on mouse Ch10 influences susceptibility to limbic seizure severity: Fine mapping and in silico candidate gene analysis

Genes, Brain and Behavior

Volumn 13, Issue 3, 2014, Pages 341-349

  Winawer, M R ^a,b   Klassen, T L ^c   Teed, S ^b   Shipman, M ^b   Leung, E H ^a   Palmer, A A ^a,d  

^a Department of Neurology ^*  (United States)

^b Taub Institute for Research on Alzheimer's Disease and the Aging Brain and the Gertrude H Sergievsky Center   (United States)

^c UNIVERSITY OF BRITISH COLUMBIA   (Canada)

^d UNIVERSITY OF CHICAGO   (United States)

Author keywords

Anxiety; Bioinformatics; Comorbidity; ECT; Epilepsy; Genetics; in silico; Mouse; Pilocarpine; Seizure

Indexed keywords

4 AMINOBUTYRIC ACID RECEPTOR; BIOLOGICAL MARKER; CS PROTEIN; CYCLIN DEPENDENT KINASE 2; GLS2 PROTEIN; PAN2 PROTEIN; PILOCARPINE; STAT2 PROTEIN; UNCLASSIFIED DRUG;

ARTICLE; C57BL 6 MOUSE; CHROMOSOME 10; COMPLEX PARTIAL SEIZURE; COMPUTER MODEL; DISEASE SEVERITY; DRUG SENSITIVITY; ELECTROCONVULSIVE THRESHOLD; EMBRYO DEVELOPMENT; EPILEPTIC STATE; GENE LOCUS; GENE MAPPING; GENETIC ANALYSIS; GENETIC SUSCEPTIBILITY; MOUSE; NERVE CELL DIFFERENTIATION; NERVE EXCITABILITY; NONHUMAN; PRIORITY JOURNAL; SEIZURE SUSCEPTIBILITY; SEIZURE THRESHOLD;

ANXIETY; BIOINFORMATICS; COMORBIDITY; ECT; EPILEPSY; GENETICS; IN SILICO; MOUSE; PILOCARPINE; SEIZURE;

ANIMALS; CHROMOSOME MAPPING; CHROMOSOMES, HUMAN, PAIR 12; CHROMOSOMES, MAMMALIAN; COMPUTATIONAL BIOLOGY; GENETIC LOCI; GENETIC PREDISPOSITION TO DISEASE; HUMANS; MICE; MICE, CONGENIC; MICE, INBRED C57BL; PILOCARPINE; SEIZURES;

EID: 84896816656     PISSN: 16011848     EISSN: 1601183X     Source Type: Journal    
DOI: 10.1111/gbb.12116     Document Type: Article

References (67)

1. Basel-Vanagaite, L., Hershkovitz, T., Heyman, E. et al. (2013) Biallelic SZT2 mutations cause infantile encephalopathy with epilepsy and dysmorphic corpus callosum. Am J Hum Genet 93, 524-529.
2. Bergren, S.K., Rutter, E.D. & Kearney, J.A. (2009) Fine mapping of an epilepsy modifier gene on mouse Chromosome 19. Mamm Genome 20, 359-366.
3. Bockenhauer, D., Feather, S., Stanescu, H.C. et al. (2009) Epilepsy, ataxia, sensorineural deafness, tubulopathy, and KCNJ10 mutations. N Engl J Med 360, 1960-1970.
4. Borges, K., Gearing, M., Mcdermott, D.L., Smith, A.B., Almonte, A.G., Wainer, B.H. & Dingledine, R. (2003) Neuronal and glial pathological changes during epileptogenesis in the mouse pilocarpine model. Exp Neurol 182, 21-34.
5. Brooks-Kayal, A.R., Raol, Y.H. & Russek, S.J. (2009) Alteration of epileptogenesis genes. Neurotherapeutics 6, 312-318.
6. Buono, R.J., Lohoff, F.W., Sander, T., Sperling, M.R., O'Connor, M.J., Dlugos, D.J., Ryan, S.G., Golden, G.T., Zhao, H., Scattergood, T.M., Berrettini, W.H. & Ferraro, T.N. (2004) Association between variation in the human KCNJ10 potassium ion channel gene and seizure susceptibility. Epilepsy Res 58, 175-183.
7. Chaix, Y., Ferraro, T.N., Lapouble, E. & Martin, B. (2007) Chemoconvulsant-induced seizure susceptibility: toward a common genetic basis? Epilepsia 48 (Suppl. 5), 48-52.
8. Dibbens, L.M., Heron, S.E. & Mulley, J.C. (2007) A polygenic heterogeneity model for common epilepsies with complex genetics. Genes Brain Behav 6, 593-597.
9. Engstrom, F.L. & Woodbury, D.M. (1988) Seizure susceptibility in DBA and C57 mice: the effects of various convulsants. Epilepsia 29, 389-395.
10. Ferraro, T.N., Golden, G.T., Smith, G.G. & Berrettini, W.H. (1995) Differential susceptibility to seizures induced by systemic kainic acid treatment in mature DBA/2J and C57BL/6J mice. Epilepsia 36, 301-307.
11. Ferraro, T.N., Golden, G.T., Snyder, R., Laibinis, M., Smith, G.G., Buono, R.J. & Berrettini, W.H. (1998) Genetic influences on electrical seizure threshold. Brain Res 813, 207-210.
12. Ferraro, T.N., Golden, G.T., Smith, G.G., St Jean, P., Schork, N.J., Mulholland, N., Ballas, C., Schill, J., Buono, R.J. & Berrettini, W.H. (1999) Mapping loci for pentylenetetrazol-induced seizure susceptibility in mice. J Neurosci 19, 6733-6739.
13. Ferraro, T.N., Golden, G.T., Smith, G.G., Longman, R.L., Snyder, R.L., Demuth, D., Szpilzak, I., Mulholland, N., Eng, E., Lohoff, F.W., Buono, R.J. & Berrettini, W.H. (2001) Quantitative genetic study of maximal electroshock seizure threshold in mice: evidence for a major seizure susceptibility locus on distal chromosome 1. Genomics 75, 35-42.
14. Ferraro, T.N., Golden, G.T., Smith, G.G., Demuth, D., Buono, R.J. & Berrettini, W.H. (2002) Mouse strain variation in maximal electroshock seizure threshold. Brain Res 936, 82-86.
15. Ferraro, T.N., Golden, G.T., Smith, G.G., Martin, J.F., Lohoff, F.W., Gieringer, T.A., Zamboni, D., Schwebel, C.L., Press, D.M., Kratzer, S.O., Zhao, H., Berrettini, W.H. & Buono, R.J. (2004) Fine mapping of a seizure susceptibility locus on mouse Chromosome 1: nomination of Kcnj10 as a causative gene. Mamm Genome 15, 239-251.
16. Frankel, W.N., Taylor, L., Beyer, B., Tempel, B.L. & White, H.S. (2001) Electroconvulsive thresholds of inbred mouse strains. Genomics 74, 306-312.
17. Frankel, W.N., Yang, Y., Mahaffey, C.L., Beyer, B.J. & O'Brien, T.P. (2009) Szt2, a novel gene for seizure threshold in mice. Genes Brain Behav 8, 568-576.
18. Gershenfeld, H.K., Neumann, P.E., Li, X., St Jean, P.L. & Paul, S.M. (1999) Mapping quantitative trait loci for seizure response to a GABAA receptor inverse agonist in mice. J Neurosci 19, 3731-3738.
19. Grosso, S., Pucci, L., Farnetani, M., Di Bartolo, R.M., Galimberti, D., Mostardini, R., Anichini, C., Balestri, M., Morgese, G. & Balestri, P. (2004) Epilepsy and electroencephalographic findings in pericentric inversion of chromosome 12. J Child Neurol 19, 604-608.
20. Hain, H.S., Crabbe, J.C., Bergeson, S.E. & Belknap, J.K. (2000) 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 293, 180-187.
21. Hawkins, N.A. & Kearney, J.A. (2012) Confirmation of an epilepsy modifier locus on mouse chromosome 11 and candidate gene analysis by RNA-Seq. Genes Brain Behav 11, 452-460.
22. Helbig, I., Scheffer, I.E., Mulley, J.C. & Berkovic, S.F. (2008) Navigating the channels and beyond: unravelling the genetics of the epilepsies. Lancet Neurol 7, 231-245.
23. Jansen, L.A., Uhlmann, E.J., Crino, P.B., Gutmann, D.H. & Wong, M. (2005) Epileptogenesis and reduced inward rectifier potassium current in tuberous sclerosis complex-1-deficient astrocytes. Epilepsia 46, 1871-1880.
24. Keane, T.M., Goodstadt, L., Danecek, P. et al. (2011) Mouse genomic variation and its effect on phenotypes and gene regulation. Nature 477, 289-294.
25. Kearney, J.A., Buchner, D.A., De Haan, G., Adamska, M., Levin, S.I., Furay, A.R., Albin, R.L., Jones, J.M., Montal, M., Stevens, M.J., Sprunger, L.K. & Meisler, M.H. (2002) Molecular and pathological effects of a modifier gene on deficiency of the sodium channel Scn8a (Na(v)1.6). Hum Mol Genet 11, 2765-2775.
26. Kim, S., Zhang, S., Choi, K.H., Reister, R., Do, C., Baykiz, A.F. & Gershenfeld, H.K. (2009) An E3 ubiquitin ligase, Really Interesting New Gene (RING) Finger 41, is a candidate gene for anxiety-like behavior and beta-carboline-induced seizures. Biol Psychiatry 65, 425-431.
27. Kong, S., Lorenzana, A., Deng, Q., McNeill, T.H. & Schauwecker, P.E. (2008) Variation in Galr1 expression determines susceptibility to exocitotoxin-induced cell death in mice. Genes Brain Behav 7, 587-598.
28. Kosobud, A.E. & Crabbe, J.C. (1990) Genetic correlations among inbred strain sensitivities to convulsions induced by 9 convulsant drugs. Brain Res 526, 8-16.
29. Kwan, P. & Brodie, M.J. (2000) Early identification of refractory epilepsy. N Engl J Med 342, 314-319.
30. Leite, J.P., Garcia-Cairasco, N. & Cavalheiro, E.A. (2002) New insights from the use of pilocarpine and kainate models. Epilepsy Res 50, 93-103.
31. Lim, S. & Kaldis, P. (2012) Loss of Cdk2 and Cdk4 induces a switch from proliferation to differentiation in neural stem cells. Stem Cells 30, 1509-1520.
32. Lorenzana, A., Chancer, Z. & Schauwecker, P.E. (2007) A quantitative trait locus on chromosome 18 is a critical determinant of excitotoxic cell death susceptibility. Eur J Neurosci 25, 1998-2008.
33. Mansour, H.A., Wood, J., Logue, T., Chowdari, K.V., Dayal, M., Kupfer, D.J., Monk, T.H., Devlin, B. & Nimgaonkar, V.L. (2006) Association study of eight circadian genes with bipolar I disorder, schizoaffective disorder and schizophrenia. Genes Brain Behav 5, 150-157.
34. Margari, L., Di Cosola, M.L., Buttiglione, M., Pansini, A., Buonadonna, A.L., Craig, F., Cariola, F., Petruzzelli, M.G. & Gentile, M. (2012) Molecular cytogenetic characterization and genotype/phenotype analysis in a patient with a de novo 8p23.2p23.3 deletion/12p13.31p13.33 duplication. Am J Med Genet A 158A, 1713-1718.
35. Martin, M.S., Tang, B., Papale, L.A., Yu, F.H., Catterall, W.A. & Escayg, A. (2007) The voltage-gated sodium channel Scn8a is a genetic modifier of severe myoclonic epilepsy of infancy. Hum Mol Genet 16, 2892-2899.
36. McKhann, G.M. II, Wenzel, H.J., Robbins, C.A., Sosunov, A.A. & Schwartzkroin, P.A. (2003) Mouse strain differences in kainic acid sensitivity, seizure behavior, mortality, and hippocampal pathology. Neuroscience 122, 551-561.
37. Morar, B., Zhelyazkova, S., Azmanov, D.N., Radionova, M., Angelicheva, D., Guergueltcheva, V., Kaneva, R., Scheffer, I.E., Tournev, I., Kalaydjieva, L. & Sander, J.W. (2011) A novel GEFS+ locus on 12p13.33 in a large Roma family. Epilepsy Res 97, 198-207.
38. Mulley, J.C. & Dibbens, L.M. (2009) Chipping away at the common epilepsies with complex genetics: the 15q13.3 microdeletion shows the way. Genome Med 1, 33.
39. Neumann, P.E. & Collins, R.L. (1991) Genetic dissection of susceptibility to audiogenic seizures in inbred mice. Proc Natl Acad Sci U S A 88, 5408-5412.
40. Neumann, P.E. & Collins, R.L. (1992) Confirmation of the influence of a chromosome 7 locus on susceptibility to audiogenic seizures. Mamm Genome 3, 250-253.
41. Ottman, R. (2005) Analysis of genetically complex epilepsies. Epilepsia 46 (Suppl. 10), 7-14.
42. Ottman, R., Annegers, J.F., Risch, N., Hauser, W.A. & Susser, M. (1996) Relations of genetic and environmental factors in the etiology of epilepsy. Ann Neurol 39, 442-449.
43. Ottman, R., Hirose, S., Jain, S., Lerche, H., Lopes-Cendes, I., Noebels, J.L., Serratosa, J., Zara, F. & Scheffer, I.E. (2010) Genetic testing in the epilepsies--report of the ILAE Genetics Commission. Epilepsia 51, 655-670.
44. Otto, J.F., Yang, Y., Frankel, W.N., Wilcox, K.S. & White, H.S. (2004) Mice carrying the szt1 mutation exhibit increased seizure susceptibility and altered sensitivity to compounds acting at the m-channel. Epilepsia 45, 1009-1016.
45. Otto, J.F., Yang, Y., Frankel, W.N., White, H.S. & Wilcox, K.S. (2006) A spontaneous mutation involving Kcnq2 (Kv7.2) reduces M-current density and spike frequency adaptation in mouse CA1 neurons. J Neurosci 26, 2053-2059.
46. Parker, C.C., Sokoloff, G., Leung, E., Kirkpatrick, S.L. & Palmer, A.A. (2013) A large QTL for fear and anxiety mapped using an F cross can be dissected into multiple smaller QTLs. Genes Brain Behav 12, 714-722.
47. Racine, R.J. (1972) Modification of seizure activity by electrical stimulation. II. Motor seizure. Electroencephalogr Clin Neurophysiol 32, 281-294.
48. Reid, C.A., Berkovic, S.F. & Petrou, S. (2009) Mechanisms of human inherited epilepsies. Prog Neurobiol 87, 41-57.
49. Sala-Rabanal, M., Kucheryavykh, L.Y., Skatchkov, S.N., Eaton, M.J. & Nichols, C.G. (2010) Molecular mechanisms of EAST/SeSAME syndrome mutations in Kir4.1 (KCNJ10). J Biol Chem 285, 36040-36048.
50. Schauwecker, P.E. (2002) Modulation of cell death by mouse genotype: differential vulnerability to excitatory amino acid-induced lesions. Exp Neurol 178, 219-235.
51. Schauwecker, P.E. (2011a) Congenic strains provide evidence that a mapped locus on chromosome 15 influences excitotoxic cell death. Genes Brain Behav 10, 100-110.
52. Schauwecker, P.E. (2011b) The relevance of individual genetic background and its role in animal models of epilepsy. Epilepsy Res 97, 1-11.
53. Schauwecker, P.E., Williams, R.W. & Santos, J.B. (2004) Genetic control of sensitivity to hippocampal cell death induced by kainic acid: a quantitative trait loci analysis. J Comp Neurol 477, 96-107.
54. Sprunger, L.K., Escayg, A., Tallaksen-Greene, S., Albin, R.L. & Meisler, M.H. (1999) Dystonia associated with mutation of the neuronal sodium channel Scn8a and identification of the modifier locus Scnm1 on mouse chromosome 3. Hum Mol Genet 8, 471-479.
55. Swinyard, E. (1972a) Electrically Induced Convulsions. Raven Press, New York.
56. Swinyard, E.A. (1972b) Electrically induced convulsions. In PURPURA, D., PENRY, J. & TOWER, D. (eds), Experimental Models of Epilepsy--A Manual for the Laboratory Worker. Raven Press, New York.
57. Tokuda, S., Mahaffey, C.L., Monks, B., Faulkner, C.R., Birnbaum, M.J., Danzer, S.C. & Frankel, W.N. (2011) A novel Akt3 mutation associated with enhanced kinase activity and seizure susceptibility in mice. Hum Mol Genet 20, 988-999.
58. Turski, W.A. (2000) Pilocarpine-induced seizures in rodents--17 years on. Pol J Pharmacol 52, 63-65.
59. Turski, L., Ikonomidou, C., Turski, W.A., Bortolotto, Z.A. & Cavalheiro, E.A. (1989) Review: cholinergic mechanisms and epileptogenesis. The seizures induced by pilocarpine: a novel experimental model of intractable epilepsy. Synapse 3, 154-171.
60. Vaglio, A., Milunsky, A., Huang, X.L., Quadrelli, A., Mechoso, B. & Quadrelli, R. (2007) A fourteen years follow-up of a case of partial trisomy 12q and monosomy 12p recombinants of a familial pericentric inversion of chromosome 12: clinical, cytogenetic and molecular observations. Eur J Med Genet 50, 224-232.
61. White, H.S., Johnson, M., Wolf, H.H. & Kupferberg, H.J. (1995) The early identification of anticonvulsant activity: role of the maximal electroshock and subcutaneous pentylenetetrazol seizure models. Ital J Neurol Sci 16, 73-77.
62. Winawer, M.R., Kuperman, R., Niethammer, M., Sherman, S., Rabinowitz, D., Guell, I.P., Ponder, C.A. & Palmer, A.A. (2007a) Use of chromosome substitution strains to identify seizure susceptibility loci in mice. Mamm Genome 18, 23-31.
63. Winawer, M.R., Makarenko, N., Mccloskey, D.P., Hintz, T.M., Nair, N., Palmer, A.A. & Scharfman, H.E. (2007b) Acute and chronic responses to the convulsant pilocarpine in DBA/2J and A/J mice. Neuroscience 149, 465-475.
64. Winawer, M.R., Gildersleeve, S.S., Phillips, A.G., Rabinowitz, D. & Palmer, A.A. (2011) Mapping a mouse limbic seizure susceptibility locus on chromosome 10. Epilepsia 52, 2076-2083.
65. Yalcin, B., Wong, K., Agam, A., Goodson, M., Keane, T.M., Gan, X., Nellaker, C., Goodstadt, L., Nicod, J., Bhomra, A., Hernandez-Pliego, P., Whitley, H., Cleak, J., Dutton, R., Janowitz, D., Mott, R., Adams, D.J. & Flint, J. (2011) Sequence-based characterization of structural variation in the mouse genome. Nature 477, 326-329.
66. Yang, Y., Beyer, B.J., Otto, J.F., O'Brien, T.P., Letts, V.A., White, H.S. & Frankel, W.N. (2003) Spontaneous deletion of epilepsy gene orthologs in a mutant mouse with a low electroconvulsive threshold. Hum Mol Genet 12, 975-984.
67. Zhang, S., Lou, Y., Amstein, T.M., Anyango, M., Mohibullah, N., Osoti, A., Stancliffe, D., King, R., Iraqi, F. & Gershenfeld, H.K. (2005) Fine mapping of a major locus on chromosome 10 for exploratory and fear-like behavior in mice. Mamm Genome 16, 306-318.