Advances on genetic rat models of epilepsy

Experimental Animals

Volumn 64, Issue 1, 2015, Pages 1-17

  Serikawa, Tadao ^a,b   Mashimo, Tomoji ^a   Kuramoto, Takashi ^a   Voigt, Birger ^a   Ohno, Yukihiro ^b   Sasa, Masashi ^c  

^a KYOTO UNIVERSITY   (Japan)

^b OSAKA MEDICAL COLLEGE   (Japan)

^c Nagisa Clinic   (Japan)

Author keywords

Antiepileptic drug (AED); ENU mutagenesis; Epileptic rat model; Epileptogenesis; Spontaneous mutation

Indexed keywords

4 AMINOBUTYRIC ACID; 4 AMINOBUTYRIC ACID A RECEPTOR; ANTICONVULSIVE AGENT; ASPARTOACYLASE; BENZODIAZEPINE RECEPTOR; BRAIN DERIVED NEUROTROPHIC FACTOR; CARBAMAZEPINE; CLOBAZAM; CLONAZEPAM; DIAZEPAM; ECDYSTERONE; ETHOSUXIMIDE; ETHYLNITROSOUREA; ETIRACETAM; HYPERPOLARIZATION ACTIVATED CYCLIC NUCLEOTIDE GATED CHANNEL; LAMOTRIGINE; MESSENGER RNA; METHYLNITROSOUREA; MUSCARINIC RECEPTOR; N METHYL DEXTRO ASPARTIC ACID RECEPTOR; PHENOBARBITAL; PHENYTOIN; TOPIRAMATE; TRIMETHADIONE; UNINDEXED DRUG; VALPROIC ACID; VANILLOID RECEPTOR 1; VANILLOID RECEPTOR 2; VIGABATRIN; ZONISAMIDE; KCNA1 PROTEIN, RAT; LGI1 PROTEIN, RAT; POTASSIUM CHANNEL KV1.1; PROTEIN; SCN1A PROTEIN, RAT; SODIUM CHANNEL NAV1.1;

ANTICONVULSANT ACTIVITY; ATAXIA; AUDIOGENIC SEIZURE; CACNA1A GENE; CANAVAN DISEASE; CHEMICAL MUTAGENESIS; COMPARATIVE GENOMIC HYBRIDIZATION; DISEASE COURSE; ELECTROENCEPHALOGRAM; ELECTROSHOCK SEIZURE; EPILEPSY; EPILEPTOGENESIS; FEBRILE CONVULSION; GENE; GENE MUTATION; GENETIC MODEL; LGI1 GENE; MYOKYMIA; NONHUMAN; QUALITY OF LIFE; RATTUS NORVEGICUS; REVIEW; SEVERE MYOCLONIC EPILEPSY IN INFANCY; SINGLE NUCLEOTIDE POLYMORPHISM; TEMPORAL LOBE EPILEPSY; TONIC CLONIC SEIZURE; ANIMAL; BIOLOGICAL MODEL; DISEASE MODEL; GENETIC ENGINEERING; GENETIC PREDISPOSITION; GENETICS; GENOME; MISSENSE MUTATION; MUTAGENESIS; PHENOTYPE; PROCEDURES; RAT; TRENDS;

RATTUS; RATTUS NORVEGICUS;

ANIMALS; DISEASE MODELS, ANIMAL; EPILEPSY; ETHYLNITROSOUREA; GENETIC ENGINEERING; GENETIC PREDISPOSITION TO DISEASE; GENOME; KV1.1 POTASSIUM CHANNEL; MODELS, GENETIC; MUTAGENESIS; MUTATION, MISSENSE; NAV1.1 VOLTAGE-GATED SODIUM CHANNEL; PHENOTYPE; PROTEINS; RATS;

EID: 84922250148     PISSN: 13411357     EISSN: None     Source Type: Journal    
DOI: 10.1538/expanim.14-0066     Document Type: Review

References (127)

1. Aitman, T.J., Critser, J.K., Cuppen, E., Dominiczak, A., Fernandez- Suarez, X.M., Flint, J., Gauguier, D., Geurts, A.M., Gould, M., Harris, P.C., Holmdahl, R., Hubner, N., Izsvák, Z., Jacob, H.J., Kuramoto, T., Kwitek, A.E., Marrone, A., Mashimo, T., Moreno, C., Mullins, J., Mullins, L., Olsson, T., Pravenec, M., Riley, L., Saar, K., Serikawa, T., Shull, J.D., Szpirer, C., Twigger, S.N., Voigt, B., and Worley, K. 2008. Progress and prospects in rat genetics: a community view. Nat. Genet. 40: 516-522. [Medline] [CrossRef]
2. A kimitsu, T., Kurisu, K., Hanaya, R., Iida, K., Kiura, Y., Arita, K., Matsubayashi, H., Ishihara, K., Kitada, K., Serikawa, T., and Sasa, M. 2000. Epileptic seizures induced by N-acetyl- L-aspartate in rats: in vivo and in vitro studies. Brain Res. 861: 143-150. [Medline] [CrossRef]
3. Akman, O., Demiralp, T., Ates, N., and Onat, F.Y. 2010. Electroencephalographic differences between WAG /Rij and GAERS rat models of absence epilepsy. Epilepsy Res. 89: 185-193. [Medline] [CrossRef]
4. A mano, H., Amano, T., Matsubayashi, H., Ishihara, K., Serikawa, T., and Sasa, M. 2001. Enhanced calcium influx in hippocampal CA3 neurons of spontaneously epileptic rats. Epilepsia 42: 345-350. [Medline] [CrossRef]
5. A mano, S., Ihara, N., Uemura, S., Yokoyama, M., Ikeda, M., Serikawa, T., Sasahara, M., Kataoka, H., Hayase, Y., and Hazama, F. 1996. Development of a novel rat mutant with spontaneous limbic-like seizures. Am. J. Pathol. 149: 329-336. [Medline]
6. A mano, T., Aihua, Z., Matsubayashi, H., Seki, T., Serikawa, T., Sasa, M., and Sakai, N. 2004. Antiepileptic effects of single and repeated oral administrations of S-312-d, a novel calcium channel antagonist, on tonic convulsions in spontaneously epileptic rats. J. Pharmacol. Sci. 95: 355-362. [Medline] [CrossRef]
7. A mano, T., Amano, H., Matsubayashi, H., Ishihara, K., Serikawa, T., and Sasa, M. 2001. Enhanced Ca2+ influx with mossy fiber stimulation in hippocampal CA3 neurons of spontaneously epileptic rats. Brain Res. 910: 199-203. [Medline] [CrossRef]
8. Amano, T., Matsubayashi, H., Ozkan, E.D., Sasa, M., Serikawa, T., and Ueda, T. 2002. Aberrant reduction of an inhibitory protein factor in a rat epileptic model. Epilepsy Res. 51: 81-91. [Medline] [CrossRef]
9. A rai, M., Amano, S., Ryo, A., Hada, A., Wakatsuki, T., Shuda, M., Kondoh, N., and Yamamoto, M. 2003. Identification of epilepsy-related genes by gene expression profiling in the hippocampus of genetically epileptic rat. Brain Res. Mol. Brain Res. 118: 147-151. [Medline] [CrossRef]
10. A sano, Y., Serikawa, T., and Yamada, J. 1994. Improvement of poor operant performance by continual intake of phenobarbital in spontaneously epileptic rats. Jikken Dobutsu 43: 137-140. [Medline]
11. A tanur, S.S., Diaz, A.G., Maratou, K., Sarkis, A., Rotival, M., Game, L., Tschannen, M.R., Kaisaki, P.J., Otto, G.W., Ma, M.C., Keane, T.M., Hummel, O., Saar, K., Chen, W., Guryev, V., Gopalakrishnan, K., Garrett, M.R., Joe, B., Citterio, L., Bianchi, G., McBride, M., Dominiczak, A., Adams, D.J., Serikawa, T., Flicek, P., Cuppen, E., Hubner, N., Petretto, E., Gauguier, D., Kwitek, A., Jacob, H., and Aitman, T.J. 2013. Genome sequencing reveals loci under artificial selection that underlie disease phenotypes in the laboratory rat. Cell 154: 691-703. [Medline] [CrossRef]
12. Baraban, S.C., Dinday, M.T., and Hortopan, G.A. 2013. Drug screening in Scn1a zebrafish mutant identifies clemizole as a potential Dravet syndrome treatment. Nat. Commun. 4: 2410. [Medline] [CrossRef]
13. Baslow, M.H., Kitada, K., Suckow, R.F., Hungund, B.L., and Serikawa, T. 2002. The effects of lithium chloride and other substances on levels of brain N-acetyl-L-aspartic acid in Canavan disease-like rats. Neurochem. Res. 27: 403-406. [Medline] [CrossRef]
14. Baud, A., Hermsen, R., Guryev, V., Stridh, P., Graham, D., McBride, M.W., Foroud, T., Calderari, S., Diez, M., Ockinger, J., Beyeen, A.D., Gillett, A., Abdelmagid, N., Guerreiro- Cacais, A.O., Jagodic, M., Tuncel, J., Norin, U., Beattie, E., Huynh, N., Miller, W.H., Koller, D.L., Alam, I., Falak, S., Osborne-Pellegrin, M., Martinez-Membrives, E., Canete, T., Blazquez, G., Vicens-Costa, E., Mont-Cardona, C., Diaz-Moran, S., Tobena, A., Hummel, O., Zelenika, D., Saar, K., Patone, G., Bauerfeind, A., Bihoreau, M.T., Heinig, M., Lee, Y.A., Rintisch, C., Schulz, H., Wheeler, D.A., Worley, K.C., Muzny, D.M., Gibbs, R.A., Lathrop, M., Lansu, N., Toonen, P., Ruzius, F.P., de Bruijn, E., Hauser, H., Adams, D.J., Keane, T., Atanur, S.S., Aitman, T.J., Flicek, P., Malinauskas, T., Jones, E.Y., Ekman, D., Lopez-Aumatell, R., Dominiczak, A.F., Johannesson, M., Holmdahl, R., Olsson, T., Gauguier, D., Hubner, N., Fernandez-Teruel, A., Cuppen, E., Mott, R., Flint, J., Rat Genome Sequencing and Mapping Consortium 2013. Combined sequence-based and genetic mapping analysis of complex traits in outbred rats. Nat. Genet. 45: 767-775. [Medline] [CrossRef]
15. Baulac, S. and Baulac, M. 2010. Advances on the genetics of Mendelian idiopathic epilepsies. Clin. Lab. Med. 30: 911- 929. [Medline] [CrossRef]
16. Baulac, S., Ishida, S., Mashimo, T., Boillot, M., Fumoto, N., Kuwamura, M., Ohno, Y., Takizawa, A., Aoto, T., Ueda, M., Ikeda, A., LeGuern, E., Takahashi, R., and Serikawa, T. 2012. A rat model for LGI1-related epilepsies. Hum. Mol. Genet. 21: 3546-3557. [Medline] [CrossRef]
17. Ji-qun, C., Ishihara, K., Nagayama, T., Serikawa, T., and Sasa, M. 2005. Long-lasting antiepileptic effects of levetiracetam against epileptic seizures in the spontaneously epileptic rat (SER): differentiation of levetiracetam from conventional antiepileptic drugs. Epilepsia 46: 1362-1370. [Medline] [CrossRef]
18. Dailey, J.W. and Jobe, P.C. 1985. Anticonvulsant drugs and the genetically epilepsy-prone rat. Fed. Proc. 44: 2640- 2644. [Medline]
19. Dezsi, G., Ozturk, E., Stanic, D., Powell, K.L., Blumenfeld, H., O'Brien, T.J., and Jones, N.C. 2013. Ethosuximide reduces epileptogenesis and behavioral comorbidity in the GAERS model of genetic generalized epilepsy. Epilepsia 54: 635-643. [Medline] [CrossRef]
20. Díaz-Morán, S., Palència, M., Mont-Cardona, C., Cañete, T., Blázquez, G., Martínez-Membrives, E., López-Aumatell, R., Sabariego, M., Donaire, R., Morón, I., Torres, C., Martínez- Conejero, J.A., Tobeña, A., Esteban, F.J., and Fernández- Teruel, A. 2013. Gene expression in hippocampus as a function of differential trait anxiety levels in genetically heterogeneous NIH-HS rats. Behav. Brain Res. 257: 129-139. [Medline] [CrossRef]
21. E bert, U., Reissmüller, E., and Löscher, W. 2000. The new antiepileptic drugs lamotrigine and felbamate are effective in phenytoin-resistant kindled rats. Neuropharmacology 39: 1893-1903. [Medline] [CrossRef]
22. Engel, J. Jr., Pitkänen, A., Loeb, J.A., Dudek, F.E., Bertram, E.H. 3rd., Cole, A.J., Moshé, S.L., Wiebe, S., Jensen, F.E., Mody, I., Nehlig, A., and Vezzani, A. 2013. Epilepsy biomarkers. Epilepsia 54:(Suppl 4): 61-69. [Medline] [Cross- Ref]
23. Faingold, C.L. 2002. Role of GABA abnormalities in the inferior colliculus pathophysiology - audiogenic seizures. Hear. Res. 168: 223-237. [Medline] [CrossRef]
24. Frankel, W.N. 2009. Genetics of complex neurological disease: challenges and opportunities for modeling epilepsy in mice and rats. Trends Genet. 25: 361-367. [Medline] [CrossRef]
25. Fukao, K., Momiyama, T., Ishihara, K., Ujihara, H., Fujita, Y., Taniyama, K., Serikawa, T., and Sasa, M. 1998. Inhibition by gamma-aminobutyric acid system activation of epileptic seizures in spontaneously epileptic rats. Jpn. J. Pharmacol. 76: 387-396. [Medline] [CrossRef]
26. Fumoto, N., Mashimo, T., Masui, A., Ishida, S., Mizuguchi, Y., Minamimoto, S., Ikeda, A., Takahashi, R., Serikawa, T., and Ohno, Y. 2014. Evaluation of seizure foci and genes in the Lgi1L385R/+ mutant rat. Neurosci. Res. 80: 69-75. [Medline] [CrossRef]
27. G auguier, D., van Luijtelaar, G., Bihoreau, M.T., Wilder, S.P., Godfrey, R.F., Vossen, J., Coenen, A., and Cox, R.D.2004. Chromosomal mapping of genetic loci controlling absence epilepsy phenotypes in the WAG /Rij rat. Epilepsia 45: 908-915. [Medline] [CrossRef]
28. Gohma, H., Kuramoto, T., Matalon, R., Surendran, S., Tyring, S., Kitada, K., Sasa, M., and Serikawa, T. 2007. Absence- like and tonic seizures in aspartoacylase/attractin double-mutant mice. Exp. Anim. 56: 161-165. [Medline] [CrossRef]
29. Griffiths, W.J. Jr. 1944. Absence of audiogenic seizures in wild Norway and Alexandrine rats. Science 99: 62-63. [Medline] [CrossRef]
30. Guo, F., Xu, X., Cai, J., Hu, H., Sun, W., He, G., Shao, D., Wang, L., Chen, T., Shaw, C., Zhu, T., and Hao, L. 2013. The up-regulation of voltage-gated sodium channels subtypes coincides with an increased sodium current in hippocampal neuronal culture model. Neurochem. Int. 62: 287-295. [Medline] [CrossRef]
31. H anaya, R., Kiura, Y., Kurisu, K., Sakai, N., Serikawa, T., and Sasa, M. 2008. N-acetyl-L-aspartate activates hippocampal CA3 neurons in rodent slice preparations. Brain Res. Bull. 75: 663-667. [Medline] [CrossRef]
32. H anaya, R., Kiura, Y., Serikawa, T., Kurisu, K., Arita, K., and Sasa, M. 2011. Modulation of abnormal synaptic transmission in hippocampal CA3 neurons of spontaneously epileptic rats (SERs) by levetiracetam. Brain Res. Bull. 86: 334-339. [Medline] [CrossRef]
33. H anaya, R., Sasa, M., Ishihara, K., Akimitsu, T., Iida, K., Amano, T., Serikawa, T., Arita, K., and Kurisu, K. 1997. Antiepileptic effects of 20-hydroxyecdysone on convulsive seizures in spontaneously epileptic rats. Jpn. J. Pharmacol. 74: 331-335. [Medline] [CrossRef]
34. H anaya, R., Sasa, M., Kiura, Y., Ishihara, K., Serikawa, T., and Kurisu, K. 2002. Epileptiform burst discharges in hippocampal CA3 neurons of young but not mature Noda epileptic rats (NER). Brain Res. 950: 317-320. [Medline] [CrossRef]
35. H anaya, R., Sasa, M., Kiura, Y., Serikawa, T., and Kurisu, K. 2002. Effects of vigabatrin on epileptiform abnormal discharges in hippocampal CA3 neurons of spontaneously epileptic rats (SER). Epilepsy Res. 50: 223-231. [Medline] [CrossRef]
36. H anaya, R., Sasa, M., Sugata, S., Tokudome, M., Serikawa, T., Kurisu, K., and Arita, K. 2010. Hippocampal cell loss and propagation of abnormal discharges accompanied with the expression of tonic convulsion in the spontaneously epileptic rat. Brain Res. 1328: 171-180. [Medline] [CrossRef]
37. Hanaya, R., Sasa, M., Ujihara, H., Fujita, Y., Amano, T., Matsubayashi, H., Serikawa, T., and Uozumi, T. 1995. Effect of antiepileptic drugs on absence-like seizures in the tremor rat. Epilepsia 36: 938-942. [Medline] [CrossRef]
38. Hanaya, R., Sasa, M., Ujihara, H., Ishihara, K., Serikawa, T., Iida, K., Akimitsu, T., Arita, K., and Kurisu, K. 1998. Suppression by topiramate of epileptiform burst discharges in hippocampal CA3 neurons of spontaneously epileptic rat in vitro. Brain Res. 789: 274-282. [Medline] [CrossRef]
39. H arada, Y., Nagao, Y., Shimizu, S., Serikawa, T., Terada, R., Fujimoto, M., Okuda, A., Mukai, T., Sasa, M., Kurachi, Y., and Ohno, Y. 2013. Expressional analysis of inwardly rectifying Kir4.1 channels in Noda epileptic rat (NER). Brain Res. 1517: 141-149. [Medline] [CrossRef]
40. H ashimoto, R., Voigt, B., Ishimaru, Y., Hokao, R., Chiba, S., Serikawa, T., Sasa, M., and Kuramoto, T. 2013. Identification of QTLs involved in the development of amygdala kindling in the rat. Exp. Anim. 62: 181-187. [Medline] [Cross- Ref]
41. H ayashi, K., Ueshima, S., Ouchida, M., Mashimo, T., Nishiki, T., Sendo, T., Serikawa, T., Matsui, H., and Ohmori, I. 2011. Therapy for hyperthermia-induced seizures in Scn1a mutant rats. Epilepsia 52: 1010-1017. [Medline] [CrossRef]
42. H egde, M. and Lowenstein, D.H. 2014. The search for circulating epilepsy biomarkers. Biomarkers Med. 8: 413-427. [Medline] [CrossRef]
43. H igashiguchi, T., Serikawa, T., Yamada, T., Kogishi, K., Kondo, A., and Yamada, J. 1991. Semidominant expression of absence-like seizure in tremor rats. Behav. Genet. 21: 537-545. [Medline] [CrossRef]
44. I ida, K., Sasa, M., Serikawa, T., Noda, A., Ishihara, K., Akimitsu, T., Hanaya, R., Arita, K., and Kurisu, K. 1998. Induction of convulsive seizures by acoustic priming in a new genetically defined model of epilepsy (Noda epileptic rat: NER). Epilepsy Res. 30: 115-126. [Medline] [CrossRef]
45. I noue, M., Yamamoto, A., Kaneko, Y., Noda, A., and Naito, H. 2014. Effects of conventional anticonvulsant drugs on generalized tonic-clonic seizures in Noda epileptic rats. Epilepsy Res. 108: 1158-1167 [Epub ahead of print]. [Medline] [CrossRef]
46. I nui, T., Yamamura, T., Yuasa, H., Kawai, Y., Okaniwa, A., Serikawa, T., and Yamada, J. 1990. The spontaneously epileptic rat (SER), a zitter*tremor double mutant rat: histopathological findings in the central nervous system. Brain Res. 517: 123-133. [Medline] [CrossRef]
47. I shida, S., Sakamoto, Y., Nishio, T., Baulac, S., Kuwamura, M., Ohno, Y., Takizawa, A., Kaneko, S., Serikawa, T., and Mashimo, T. 2012. Kcna1-mutant rats dominantly display myokymia, neuromyotonia and spontaneous epileptic seizures. Brain Res. 1435: 154-166. [Medline] [CrossRef]
48. Ishihara, K., Sasa, M., Momiyama, T., Ujihara, H., Nakamura, J., Serikawa, T., Yamada, J., and Takaori, S. 1993. Abnormal excitability of hippocampal CA3 pyramidal neurons of spontaneously epileptic rats (SER), a double mutant. Exp. Neurol. 119: 287-290. [Medline] [CrossRef]
49. I shimaru, Y., Chiba, S., Serikawa, T., Sasa, M., Inaba, H., Tamura, Y., Ishimoto, T., Takasaki, H., Sakamoto, K., and Yamaguchi, K. 2010. Effects of levetiracetam on hippocampal kindling in Noda epileptic rats. Brain Res. 1309: 104- 109. [Medline] [CrossRef]
50. I shishita, S., Inui, T., Matsuda, Y., Serikawa, T., and Kitada, K. 2013. Infertility associated with meiotic failure in the tremor rat (tm/tm) is caused by the deletion of spermatogenesis associated 22. Exp. Anim. 62: 219-227. [Medline] [CrossRef]
51. Jeub, M., Beck, H., Siep, E., Rüschenschmidt, C., Speckmann, E.J., Ebert, U., Potschka, H., Freichel, C., Reissmüller, E., and Löscher, W. 2002. Effect of phenytoin on sodium and calcium currents in hippocampal CA1 neurons of phenytoin-resistant kindled rats. Neuropharmacology. 42: 107-116. [Medline] [CrossRef]
52. K anda, T., Kurokawa, M., Tamura, S., Nakamura, J., Ishii, A., Kuwana, Y., Serikawa, T., Yamada, J., Ishihara, K., and Sasa, M. 1996. Topiramate reduces abnormally high extracellular levels of glutamate and aspartate in the hippocampus of spontaneously epileptic rats (SER). Life Sci. 59: 1607- 1616. [Medline] [CrossRef]
53. K itada, K., Akimitsu, T., Shigematsu, Y., Kondo, A., Maihara, T., Yokoi, N., Kuramoto, T., Sasa, M., and Serikawa, T. 2000 Accumulation of N-acetyl-L-aspartate in the brain of the tremor rat, a mutant exhibiting absence-like seizure and spongiform degeneration in the central nervous system. J. Neurochem. 74: 2512-2519. [Medline] [CrossRef]
54. K iura, Y., Hanaya, R., Serikawa, T., Kurisu, K., Sakai, N., and Sasa, M. 2003. Involvement of Ca2+ channels in abnormal excitability of hippocampal CA3 pyramidal cells in noda epileptic rats. J. Pharmacol. Sci. 91: 137-144. [Medline] [CrossRef]
55. K lugmann, M., Leichtlein, C.B., Symes, C.W., Serikawa, T., Young, D., and During, M.J. 2005. Restoration of aspartoacylase activity in CNS neurons does not ameliorate motor deficits and demyelination in a model of Canavan disease. Mol. Ther. 11: 745-753. [Medline] [CrossRef]
56. K lugmann, M., Symes, C.W., Klaussner, B.K., Leichtlein, C.B., Serikawa, T., Young, D., and During, M.J. 2003. Identification and distribution of aspartoacylase in the postnatal rat brain. Neuroreport 14: 1837-1840. [Medline] [CrossRef]
57. K ole, M.H., Bräuer, A.U., and Stuart, G.J. 2007. Inherited cortical HCN1 channel loss amplifies dendritic calcium electrogenesis and burst firing in a rat absence epilepsy model. J. Physiol. 578: 507-525. [Medline] [CrossRef]
58. Kondo, A., Nagara, H., Akazawa, K., Tateishi, J., Serikawa, T., and Yamada, J. 1991. CNS pathology in the neurological mutant rats zitter, tremor and zitter-tremor double mutant (spontaneously epileptic rat, SER). Exaggeration of clinical and neuropathological phenotypes in SER. Brain 114: 979- 999. [Medline] [CrossRef]
59. K uramoto, T., Kitada, K., Inui, T., Sasaki, Y., Ito, K., Hase, T., Kawagachi, S., Ogawa, Y., Nakao, K., Barsh, G.S., Nagao, M., Ushijima, T., and Serikawa, T. 2001. Attractin/ mahogany/zitter plays a critical role in myelination of the central nervous system. Proc. Natl. Acad. Sci. USA 98: 559-564. [Medline] [CrossRef]
60. K urtz, B.S., Lehman, J., Garlick, P., Amberg, J., Mishra, P.K., Dailey, J.W., Weber, R., and Jobe, P.C. 2001. Penetrance and expressivity of genes involved in the development of epilepsy in the genetically epilepsy-prone rat (GEPR). J. Neurogenet. 15: 233-244. [Medline] [CrossRef]
61. Löscher, W. 1984. Genetic animal models of epilepsy as a unique resource for the evaluation of anticonvulsant drugs. A review. Methods Find. Exp. Clin. Pharmacol. 6: 531-547. [Medline]
62. Löscher, W., Cramer, S., and Ebert, U. 1998. Differences in kindling development in seven outbred and inbred rat strains. Exp. Neurol. 154: 551-559. [Medline] [CrossRef]
63. Löscher, W., Klitgaard, H., Twyman, R.E., and Schmidt, D. 2013 New avenues for anti-epileptic drug discovery and development. Nat. Rev. Drug Discov. 12: 757-776. [Medline] [CrossRef]
64. Löscher, W., Reissmüller, E., and Ebert, U. 2000. Anticonvulsant efficacy of gabapentin and levetiracetam in phenytoin- resistant kindled rats. Epilepsy Res. 40: 63-77. [Medline] [CrossRef]
65. Maihara, T., Noda, A., Yamazoe, H., Voigt, B., Kitada, K., and Serikawa, T. 2000. Chromosomal mapping of genes for epilepsy in NER: a rat strain with tonic-clonic seizures. Epilepsia 41: 941-949. [Medline] [CrossRef]
66. Marescaux, C., Vergnes, M., and Depaulis, A. 1992. Genetic absence epilepsy in rats from Strasbourg-a review. J. Neural Transm. Suppl. 35: 37-69. [Medline]
67. Mashimo, T., Takizawa, A., Voigt, B., Yoshimi, K., Hiai, H., Kuramoto, T., and Serikawa, T. 2010. Generation of knockout rats with X-linked severe combined immunodeficiency (X-SCID) using zinc-finger nucleases. PLoS ONE 5: e8870. [Medline] [CrossRef]
68. Mashimo, T., Ohmori, I., Ouchida, M., Ohno, Y., Tsurumi, T., Miki, T., Wakamori, M., Ishihara, S., Yoshida, T., Takizawa, A., Kato, M., Hirabayashi, M., Sasa, M., Mori, Y., and Serikawa, T. 2010. A missense mutation of the gene encoding voltage-dependent sodium channel (Nav1.1) confers susceptibility to febrile seizures in rats. J. Neurosci. 30: 5744-5753. [Medline] [CrossRef]
69. Mashimo, T., Yanagihara, K., Tokuda, S., Voigt, B., Takiza wa, A., Nakajima, R., Kato, M., Hirabayashi, M., Kuramoto, T., and Serikawa, T. 2008. An ENU-induced mutant archive for gene targeting in rats. Nat. Genet. 40: 514-515. [Medline] [CrossRef]
70. McPhee, S.W., Francis, J., Janson, C.G., Serikawa, T., Hyland, K., Ong, E.O., Raghavan, S.S., Freese, A., and Leone, P. 2005. Effects of AAV-2-mediated aspartoacylase gene transfer in the tremor rat model of Canavan disease. Brain Res. Mol. Brain Res. 135: 112-121. [Medline] [CrossRef]
71. Mitsuyoshi, I., Ito, M., Shirasaka, Y., Mikawa, H., Serikawa, T., and Yamada, J. 1993. Changes of NMDA receptor binding in spontaneously epileptic rat and parent strains. Neurochem. Res. 18: 1169-1173. [Medline] [CrossRef]
72. Miura, Y., Amano, S., Torii, R., and Ihara, N. 2002. Clobazam shows a different antiepileptic action profile from clonazepam and zonisamide in Ihara epileptic rats. Epilepsy Res. 49: 189-202. [Medline] [CrossRef]
73. Momiyama, T., Ishihara, K., Kimura, K., Todo, N., Fujita, Y., Serikawa, T., and Sasa, M. 1996. Long-term antiepileptic effects of chronic intake of CNK-602A, a thyrotropinreleasing hormone analogue, on spontaneously epileptic rats. Epilepsia 37: 328-331. [Medline] [CrossRef]
74. Momiyama, T., Ishihara, K., Serikawa, T., Moritake, K., and Sasa, M. 1995. Effect of nicardipine on abnormal excitability of CA3 pyramidal cells in hippocampal slices of spontaneously epileptic rats. Eur. J. Pharmacol. 280: 119-123. [Medline] [CrossRef]
75. Murase, K., Nabeshima, T., Kameyama, T., Sasa, M., Takaori, S., Ujihara, H., Ishihara, K., Yamada, J., and Serikawa, T. 1991. Characteristics of muscarinic cholinergic, gammaaminobutyric acidA and phencyclidine receptors in spontaneously epileptic rats; in vitro quantitative autoradiographic analysis. Neurosci. Lett. 131: 1-4. [Medline] [CrossRef]
76. N akamura, J., Tamura, S., Kanda, T., Ishii, A., Ishihara, K., Serikawa, T., Yamada, J., and Sasa, M. 1994. Inhibition by topiramate of seizures in spontaneously epileptic rats and DBA/2 mice. Eur. J. Pharmacol. 254: 83-89. [Medline] [CrossRef]
77. N ava, C., Dalle, C., Rastetter, A., Striano, P., de Kovel, C.G., Nabbout, R., Cancès, C., Ville, D., Brilstra, E.H., Gobbi, G., Raffo, E., Bouteiller, D., Marie, Y., Trouillard, O., Robbiano, A., Keren, B., Agher, D., Roze, E., Lesage, S., Nicolas, A., Brice, A., Baulac, M., Vogt, C., El Hajj, N., Schneider, E., Suls, A., Weckhuysen, S., Gormley, P., Lehesjoki, A.E., De Jonghe, P., Helbig, I., Baulac, S., Zara, F., Koeleman, B.P., Haaf, T., LeGuern, E., Depienne, C., EuroEPINOMICS RES Consortium 2014. De novo mutations in HCN1 cause early infantile epileptic encephalopathy. Nat. Genet. 46: 640-645. [Medline] [CrossRef]
78. Noda, A., Hashizume, R., Maihara, T., Tomizawa, Y., Ito, Y., Inoue, M., Kobayashi, K., Asano, Y., Sasa, M., and Serikawa, T. 1998. NER rat strain: a new type of genetic model in epilepsy research. Epilepsia 39: 99-107. [Medline] [Cross- Ref]
79. O hno, Y., Ishihara, S., Mashimo, T., Sofue, N., Shimizu, S., Imaoku, T., Tsurumi, T., Sasa, M., and Serikawa, T. 2011. Scn1a missense mutation causes limbic hyperexcitability and vulnerability to experimental febrile seizures. Neurobiol. Dis. 41: 261-269. [Medline] [CrossRef]
80. Ohno, Y., Shimizu, S., Harada, Y., Morishita, M., Ishihara, S., Kumafuji, K., Sasa, M., and Serikawa, T. 2009. Regional expression of Fos-like immunoreactivity following seizures in Noda epileptic rat (NER). Epilepsy Res. 87: 70-76. [Medline] [CrossRef]
81. Ohno, Y., Sofue, N., Imaoku, T., Morishita, E., Kumafuji, K., Sasa, M., and Serikawa, T. 2010. Serotonergic modulation of absence-like seizures in groggy rats: a novel rat model of absence epilepsy. J. Pharmacol. Sci. 114: 99-105. [Medline] [CrossRef]
82. Ohno, Y., Sofue, N., Ishihara, S., Mashimo, T., Sasa, M., and Serikawa, T. 2010. Scn1a missense mutation impairs GABAA receptor-mediated synaptic transmission in the rat hippocampus. Biochem. Biophys. Res. Commun. 400: 117-122. [Medline] [CrossRef]
83. Pandit, S., Jeong, J.A., Jo, J.Y., Cho, H.S., Kim, D.W., Kim, J.M., Ryu, P.D., Lee, S.Y., Kim, H.W., Jeon, B.H., and Park, J.B. 2013. Dual mechanisms diminishing tonic GABAA inhibition of dentate gyrus granule cells in Noda epileptic rats. J. Neurophysiol. 110: 95-102. [Medline] [CrossRef]
84. Peeters, B.W., Kerbusch, J.M., Coenen, A.M., Vossen, J.M., and van Luijtelaar, E.L. 1992. Genetics of spike-wave discharges in the electroencephalogram (EEG) of the WAG /Rij inbred rat strain: a classical mendelian crossbreeding study. Behav. Genet. 22: 361-368. [Medline] [CrossRef]
85. Postma, T., Krupp, E., Li, X.L., Post, R.M., and Weiss, S.R. 2000 Lamotrigine treatment during amygdala-kindled seizure development fails to inhibit seizures and diminishes subsequent anticonvulsant efficacy. Epilepsia 41: 1514- 1521 [Medline] [CrossRef]
86. Powell, K.L., Cain, S.M., Ng, C., Sirdesai, S., David, L.S., Kyi, M., Garcia, E., Tyson, J.R., Reid, C.A., Bahlo, M., Foote, S.J., Snutch, T.P., and O'Brien, T.J. 2009. A Cav3.2 T-type calcium channel point mutation has splice-variantspecific effects on function and segregates with seizure expression in a polygenic rat model of absence epilepsy. J. Neurosci. 29: 371-380. [Medline] [CrossRef]
87. Renming, X., Ishihara, K., Sasa, M., Ujihara, H., Momiyama, T., Fujita, Y., Todo, N., Serikawa, T., Yamada, J., and Takaori, S. 1992. Antiepileptic effects of CNK-602A, a novel thyrotropin-releasing hormone analog, on absencelike and tonic seizures of spontaneously epileptic rats. Eur. J. Pharmacol. 223: 185-192. [Medline] [CrossRef]
88. Robinson, P.F. and Gilmore, S.A. 1980. Spontaneous generalized spike-wave discharges in the electrocorticograms of albino rats. Brain Res. 201: 452-458. [Medline] [CrossRef]
89. Rudolf, G., Bihoreau, M.T., Godfrey, R.F., Wilder, S.P., Cox, R.D., Lathrop, M., Marescaux, C., and Gauguier, D. 2004. Polygenic control of idiopathic generalized epilepsy phenotypes in the genetic absence rats from Strasbourg (GAERS). Epilepsia 45: 301-308. [Medline] [CrossRef]
90. Russo, E., Citraro, R., Scicchitano, F., De Fazio, S., Di Paola, E.D., Constanti, A., and De Sarro, G. 2010. Comparison of the antiepileptogenic effects of an early long-term treatment with ethosuximide or levetiracetam in a genetic animal model of absence epilepsy. Epilepsia 51: 1560-1569. [Medline] [CrossRef]
91. Saar, K., Beck, A., Bihoreau, M.T., Birney, E., Brocklebank, D., Chen, Y., Cuppen, E., Demonchy, S., Dopazo, J., Flicek, P., Foglio, M., Fujiyama, A., Gut, I.G., Gauguier, D., Guigo, R., Guryev, V., Heinig, M., Hummel, O., Jahn, N., Klages, S., Kren, V., Kube, M., Kuhl, H., Kuramoto, T., Kuroki, Y., Lechner, D., Lee, Y.A., Lopez-Bigas, N., Lathrop, G.M., Mashimo, T., Medina, I., Mott, R., Patone, G., Perrier-Cornet, J.A., Platzer, M., Pravenec, M., Reinhardt, R., Sakaki, Y., Schilhabel, M., Schulz, H., Serikawa, T., Shikhagaie, M., Tatsumoto, S., Taudien, S., Toyoda, A., Voigt, B., Zelenika, D., Zimdahl, H., Hubner, N., STAR Consortium 2008. SNP and haplotype mapping for genetic analysis in the rat. Nat. Genet. 40: 560-566. [Medline] [CrossRef]
92. Sadamatsu, M., Kanai, H., Masui, A., Serikawa, T., Yamada, J., Sasa, M., and Kato, N. 1995. Altered brain contents of neuropeptides in spontaneously epileptic rats (SER) and tremor rats with absence seizures. Life Sci. 57: 523-531. [Medline] [CrossRef]
93. Sakuma, T., Ochiai, H., Kaneko, T., Mashimo, T., Tokumasu, D., Sakane, Y., Suzuki, K., Miyamoto, T., Sakamoto, N., Matsuura, S., and Yamamoto, T. 2013. Repeating pattern of non-RVD variations in DNA-binding modules enhances TALEN activity. Sci Rep 3: 3379. [Medline] [CrossRef]
94. Sasa, M., Ohno, Y., Ujihara, H., Fujita, Y., Yoshimura, M., Takaori, S., Serikawa, T., and Yamada, J. 1988. Effects of antiepileptic drugs on absence-like and tonic seizures in the spontaneously epileptic rat, a double mutant rat. Epilepsia 29: 505-513. [Medline] [CrossRef]
95. Seki, T., Matsubayashi, H., Amano, T., Kitada, K., Serikawa, T., Sakai, N., and Sasa, M. 2002. Adenoviral gene transfer of aspartoacylase into the tremor rat, a genetic model of epilepsy, as a trial of gene therapy for inherited epileptic disorder. Neurosci. Lett. 328: 249-252. [Medline] [CrossRef]
96. Seki, T., Matsubayashi, H., Amano, T., Kitada, K., Serikawa, T., Sasa, M., and Sakai, N. 2004. Adenoviral gene transfer of aspartoacylase ameliorates tonic convulsions of spontaneously epileptic rats. Neurochem. Int. 45: 171-178. [Medline] [CrossRef]
97. Serikawa, T., Kuramoto, T., Hilbert, P., Mori, M., Yamada, J., Dubay, C.J., Lindpainter, K., Ganten, D., Guénet, J.L., Lathrop, G.M., and Beckmann, J.S. 1992. Rat gene mapping using PCR-analyzed microsatellites. Genetics 131: 701-721. [Medline]
98. Serikawa, T., Mashimo, T., Takizawa, A., Okajima, R., Maedomari, N., Kumafuji, K., Tagami, F., Neoda, Y., Otsuki, M., Nakanishi, S., Yamasaki, K., Voigt, B., and Kuramoto, T. 2009 National BioResource Project-Rat and related activities. Exp. Anim. 58: 333-341. [Medline] [CrossRef]
99. Serikawa, T., Ohno, Y., Sasa, M., Yamada, J., and Takaori, S. 1987 A new model of petit mal epilepsy: spontaneous spike and wave discharges in tremor rats. Lab. Anim. 21: 68-71. [Medline] [CrossRef]
100. Serikawa, T. and Yamada, J. 1986. Epileptic seizures in rats homozygous for two mutations, zitter and tremor. J. Hered. 77: 441-444. [Medline]
101. Shirasaka, Y., Ito, M., Mitsuyoshi, I., Mikawa, H., Serikawa, T., and Yamada, J. 1991. Benzodiazepine receptor binding in the spontaneously epileptic rat and its parent strains. Exp. Neurol. 113: 255-259. [Medline] [CrossRef]
102. Srivastava, A.K. and White, H.S. 2013. Carbamazepine, but not valproate, displays pharmacoresistance in lamotrigineresistant amygdala kindled rats. Epilepsy Res. 104: 26-34. [Medline] [CrossRef]
103. Steinhoff, B.J., Scholly, J., Dentel, C., and Staack, A.M. 2013 Is routine electroencephalography (EEG) a useful biomarker for pharmacoresistant epilepsy? Epilepsia 54:(Suppl 2): 63-66. [Medline] [CrossRef]
104. Sugata, S., Hanaya, R., Kumafuji, K., Tokudome, M., Serikawa, T., Kurisu, K., Arita, K., and Sasa, M. 2011. Neuroprotective effect of levetiracetam on hippocampal sclerosis-like change in spontaneously epileptic rats. Brain Res. Bull. 86: 36-41. [Medline] [CrossRef]
105. Takahashi, Y., Tsunashima, K., Sadamatsu, M., Schwarzer, C., Amano, S., Ihara, N., Sasa, M., Kato, N., and Sperk, G. 2000 Altered hippocampal expression of neuropeptide Y, somatostatin, and glutamate decarboxylase in Ihara's epileptic rats and spontaneously epileptic rats. Neurosci. Lett. 287: 105-108. [Medline] [CrossRef]
106. Takeda, A., Iida, M., Ando, M., Nakamura, M., Tamano, H., and Oku, N. 2013. Enhanced susceptibility to spontaneous seizures of noda epileptic rats by loss of synaptic Zn2+. PLoS ONE 8: e71372. [Medline] [CrossRef]
107. Takeuchi, I.K. and Takeuchi, Y.K. 1991. Neuronal degeneration in the striatum of the groggy rat: a new mutant with a movement disorder. Experientia 47: 1215-1218. [Medline] [CrossRef]
108. Tanaka, K., Shirakawa, H., Okada, K., Konno, M., Nakagawa, T., Serikawa, T., and Kaneko, S. 2007. Increased Ca2+ channel currents in cerebellar Purkinje cells of the ataxic groggy rat. Neurosci. Lett. 426: 75-80. [Medline] [Cross- Ref]
109. Tokuda, S., Kuramoto, T., Tanaka, K., Kaneko, S., Takeuchi, I.K., Sasa, M., and Serikawa, T. 2007. The ataxic groggy rat has a missense mutation in the P/Q-type voltage-gated Ca2+ channel alpha1A subunit gene and exhibits absence seizures. Brain Res. 1133: 168-177. [Medline] [CrossRef]
110. Tokuda, S., Sofue, N., Ohno, Y., Sasa, M., and Serikawa, T. 2010 Inhibitory effects of levetiracetam on absence seizures in a novel absence-like epilepsy animal model, Groggy rat. Brain Res. 1359: 298-303. [Medline] [CrossRef]
111. Traeger, E.C. and Rapin, I. 1998. The clinical course of Canavan disease. Pediatr. Neurol. 18: 207-212. [Medline] [CrossRef]
112. Tsubota, Y., Miyashita, E., Miyajima, M., Owada-Makabe, K., Yukawa, K., and Maeda, M. 2003. The Wakayama epileptic rat (WER), a new mutant exhibiting tonic-clonic seizures and absence-like seizures. Exp. Anim. 52: 53-62. [Medline] [CrossRef]
113. Tsuji, A., Amano, S., Yokoyama, M., Fukuoka, J., Hayase, Y., and Matsuda, M. 2001. Neuronal microdysgenesis and acquired lesions of the hippocampal formation connected with seizure activities in Ihara epileptic rat. Brain Res. 901: 1-11. [Medline] [CrossRef]
114. Ujihara, H., Xie, R.M., Sasa, M., Ishihara, K., Fujita, Y., Yoshimura, M., Kishimoto, T., Serikawa, T., Yamada, J., and Takaori, S. 1991. Inhibition by thyrotropin-releasing hor mone of epileptic seizures in spontaneously epileptic rats. Eur. J. Pharmacol. 196: 15-19. [Medline] [CrossRef]
115. van Boxtel, R., Toonen, P.W., Verheul, M., van Roekel, H.S., Nijman, I.J., Guryev, V., and Cuppen, E. 2008. Improved generation of rat gene knockouts by target-selected mutagenesis in mismatch repair-deficient animals. BMC Genomics 9: 460. [Medline] [CrossRef]
116. van Luijtelaar, E.L. and Coenen, A.M. 1986. Two types of electrocortical paroxysms in an inbred strain of rats. Neurosci. Lett. 70: 393-397. [Medline] [CrossRef]
117. van Luijtelaar, G., Sitnikova, E., and Littjohann, A. 2011. On the origin and suddenness of absences in genetic absence models. Clin. EEG Neurosci. 42: 83-97. [Medline] [Cross- Ref]
118. van Luijtelaar, G. and Zobeiri, M. 2014. Progress and outlooks in a genetic absence epilepsy model (WAG /Rij). Curr. Med. Chem. 21: 704-721. [Medline] [CrossRef]
119. Vergnes, M., Marescaux, C., Micheletti, G., Reis, J., Depaulis, A., Rumbach, L., and Warter, J.M. 1982. Spontaneous paroxysmal electroclinical patterns in rat: a model of generalized non-convulsive epilepsy. Neurosci. Lett. 33: 97-101. [Medline] [CrossRef]
120. Wang, J., Leone, P., Wu, G., Francis, J.S., Li, H., Jain, M.R., Serikawa, T., and Ledeen, R.W. 2009. Myelin lipid abnormalities in the aspartoacylase-deficient tremor rat. Neurochem. Res. 34: 138-148. [Medline] [CrossRef]
121. W ilcox, K.S., Dixon-Salazar, T., Sills, G.J., Ben-Menachem, E., White, H.S., Porter, R.J., Dichter, M.A., Moshé, S.L., Noebels, J.L., Privitera, M.D., and Rogawski, M.A. 2013. Issues related to development of new antiseizure treatments. Epilepsia 54:(Suppl 4): 24-34. [Medline] [CrossRef]
122. Yamada, J., Kuramoto, T., and Serikawa, T. 1994. A rat genetic linkage map and comparative maps for mouse or human homologous rat genes. Mamm. Genome 5: 63-83. [Medline] [CrossRef]
123. Yan, H.D., Ishihara, K., Serikawa, T., and Sasa, M. 2003. Activation by N-acetyl-L-aspartate of acutely dissociated hippocampal neurons in rats via metabotropic glutamate receptors. Epilepsia 44: 1153-1159. [Medline] [CrossRef]
124. Yan, H.D., Ishihara, K., Seki, T., Hanaya, R., Kurisu, K., Arita, K., Serikawa, T., and Sasa, M. 2013. Inhibitory effects of levetiracetam on the high-voltage-activated L-type Ca2+ channels in hippocampal CA3 neurons of spontaneously epileptic rat (SER). Brain Res. Bull. 90: 142-148. [Medline] [CrossRef]
125. Yan, H.D., Ji-qun, C., Ishihara, K., Nagayama, T., Serikawa, T., and Sasa, M. 2005. Separation of antiepileptogenic and antiseizure effects of levetiracetam in the spontaneously epileptic rat (SER). Epilepsia 46: 1170-1177. [Medline] [CrossRef]
126. Yokoyama, M., Amano, S., Tsuji, A., Sasahara, M., Serikawa, T., Ihara, N., Matsuda, M., Hazama, F., and Handa, J. 2001. Genetic analysis of cataract in Ihara epileptic rat. Mamm. Genome 12: 207-211. [Medline] [CrossRef]
127. Yoshimi, K., Kaneko, T., Voigt, B., and Mashimo, T. 2014. Allele-specific genome editing and correction of disease-associated phenotypes in rats using the CRISPR-Cas platform. Nat. Commun. 5: 4240. [Medline] [CrossRef]