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NON-HUMAN MAMMAL MODEL OF EPILEPSY UPDATE

外国特許コード F110002649
整理番号 S2008-0323-C0
掲載日 2011年4月6日
出願国 世界知的所有権機関(WIPO)
国際出願番号 2009JP052230
国際公開番号 WO 2009101939
国際出願日 平成21年2月10日(2009.2.10)
国際公開日 平成21年8月20日(2009.8.20)
優先権データ
  • 特願2008-031002 (2008.2.12) JP
発明の名称 (英語) NON-HUMAN MAMMAL MODEL OF EPILEPSY UPDATE
発明の概要(英語) Provided is a genuine model animal of epilepsy, since most of the existing model animals are so-called seizure model animals showing forcibly-induced seizure. Also provided is a method whereby a recombinant can be easily distinguished. A non-human mammal model of epilepsy which is an epilepsy model of a non-human animal such as rat having the same genetic defect as human genetic defect causing epilepsy, which carries a genetic mutation that is the genetic defect having been transferred into the non-human mammal DNA of neuron nicotinic acetylcholine receptor α4 subunit (CHRNA4) gene or β2 subunit (CHRNB2) gene relating to human autosomal dominant nocturnal frontal lobe epilepsy and which also carries a mutated gene obtained by transferring a specific probe thereinto. A recombinant of this non-human mammal model of epilepsy can be easily distinguished.
従来技術、競合技術の概要(英語) BACKGROUND ART
Epilepsy, about 2% people suffering from Japan is also relatively more neurological disease is, the molecular biology was unknown for a longer period. This is due to the many epilepsy is a general term for a wide variety of diseases. However, recently, little by little familial epilepsy center has been found that genetic abnormality.
Of which is an autosomal dominant nocturnal frontal lobe epilepsy, one of the 1 familial epilepsy, epileptic seizures according to an aspect of the night, its causative gene as well as abnormal receptor subunit β 2 α 4 gene wherein the mutation of CHRNA 4 and CHRNB 2 have been reported (non-patent document 1). Include a failure of the CHRNA 4 gene, S284L, 3 as well as the type of 291-292insL S280F have been reported (non-patent document 2, 3, 4, 5). Include a failure of the CHRNB 2 gene, V287L, 3 and V287M of the I312M types of a genetic abnormality that has been reported (non-patent document 6, 7, 8).
The development of epilepsy as well as diagnostic methods and the processing method as a means for the development of a so-called 'epilepsy model animal' is used. Conventional epilepsy model animal, convulsions or seizure-inducing material such as electrical stimulation using 'convulsions model animal' in. In addition, by introducing a sugar chain antibody genes cause epilepsy-like spasms of the transgenic non-human mammal is disclosed (patent document 1). In addition, ankylosing spondylitis posture conversion in response to a symptom of epilepsy or a convulsive disorder, gene function μ3B were deleted on the chromosome are also generated non-human animal (patent document 2). However, these conventional model animal, animal models of stroke and in reducing convulsions but, animal models of human molecular biology and in reducing the true epilepsy did not.
The inventors of this invention, dominant nocturnal frontal lobe epilepsy neuron human chromosome nicotinic acetylcholine receptor subunit gene α 4 284 (CHRNA 4) of the first Ser is substituted to Leu is found in (non-patent document 9).
Therefore, the inventors of the present invention, gene mutations of the CHRNA 4 receptor gene recombinant gene was introduced at a gene recombinant epilepsy model animals ate (patent document 3).
However, in the prior art, to produce a recombinant animal models of such genes in a full-size, the probability of homologous recombination to occur not high, a large number of recombinants was screened. Also, screening recombinant sequencing a portion of that gene is necessary, therefore much time and expense have been expended. Therefore, without recombinant gene sequencing method for determining if developed, can be a significant time and expense would be saved from, in the method of determining the development of such a recombinant body has been also needed.
Hirose, S., et al., Neurology 53:1749-1753, 1999
Steinlein, O.K., et al. A missense mutation in the neuronal nicotinic acetylcholine receptor alpha 4 subunit is associated with autosomal dominant nocturnal frontal lobe epilepsy. Nat Genet 11, 201-203 (1995).
Hirose, S., et al. A novel mutation of CHRNA4 responsible for autosomal dominant nocturnal frontal lobe epilepsy. Neurology 53, 1749-1753 (1999).
Steinlein, O.K., et al. Independent occurrence of the CHRNA4 Ser248Phe mutation in a Norwegian family with nocturnal frontal lobe epilepsy. Epilepsia 41, 529-535 (2000).
Steinlein, O.K., et al. An insertion mutation of the CHRNA4 gene in a family with autosomal dominant nocturnal frontal lobe epilepsy. Hum Mol Genet 6, 943-947 (1997).
De Fusco, M., et al. The nicotinic receptor b2 subunit is mutant in nocturnal frontal lobe epilepsy. Nat Genet 26, 275-276 (2000).
Phillips, H.A., et al. CHRNB2 is the second acetylcholine receptor subunit associated with autosomal dominant nocturnal frontal lobe epilepsy. Am J Hum Genet 68, 225-231 (2001).
Bertrand, D., et al. The CHRNB2 mutation I312M is associated with epilepsy and distinct memory deficits. Neurobiol Dis 20, 799-804 (2005).
Hirose, S., et al. A novel mutation of CHRNA4 responsible for autosomal dominant nocturnal frontal lobe epilepsy. Neurology 53, 1749-1753 (1999).
  • 出願人(英語)
  • ※2012年7月以前掲載分については米国以外のすべての指定国
  • Fukuoka University
  • Hirosaki University
  • 発明者(英語)
  • HIROSE, Shinichi
  • KANEKO, Sunao
国際特許分類(IPC)
指定国 National States: AE AG AL AM AO AT AU AZ BA BB BG BH BR BW BY BZ CA CH CN CO CR CU CZ DE DK DM DO DZ EC EE EG ES FI GB GD GE GH GM GT HN HR HU ID IL IN IS KE KG KM KN KP KR KZ LA LC LK LR LS LT LU LY MA MD ME MG MK MN MW MX MY MZ NA NG NI NO NZ OM PG PH PL PT RO RS RU SC SD SE SG SK SL SM ST SV SY TJ TM TN TR TT TZ UA UG US UZ VC VN ZA ZM ZW
ARIPO: BW GH GM KE LS MW MZ NA SD SL SZ TZ UG ZM ZW
EAPO: AM AZ BY KG KZ MD RU TJ TM
EPO: AT BE BG CH CY CZ DE DK EE ES FI FR GB GR HR HU IE IS IT LT LU LV MC MK MT NL NO PL PT RO SE SI SK TR
OAPI: BF BJ CF CG CI CM GA GN GQ GW ML MR NE SN TD TG

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