Genetic analyses and generation of genetic engineered animals for childhood epilepsy focusing on ion channel abnormalities

2008 Fiscal Year Final Research Report

• Project/Area Number: 18209035
• Research Category: Grant-in-Aid for Scientific Research (A)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Pediatrics
• Research Institution: Fukuoka University
• Principal Investigator: HIROSE Shinichi Fukuoka University, 医学部, 教授 (60248515)
• Co-Investigator(Renkei-kenkyūsha): MISUMI Yoshio 福岡大学, 医学部, 准教授 (10148877) ; UEHARA Akira 福岡大学, 医学部, 准教授 (60140745) ; ARAKI Kimi 熊本大学, 学内共同利用施設, 准教授 (90211705) ; SAITO Ryo 福岡大学, 薬学部, 講師 (80122696) ; TAKANO Yukio 福岡大学, 薬学部, 教授 (50113246) ; DESHIMARU Masanobu 福岡大学, 理学部, 准教授 (70309889)
• Project Period (FY): 2006 – 2008
• Keywords: 小児神経学

Research Abstract

設立・管理するてんかん遺伝子バンクを利用し、脳に発現するイオンチャネルに的を絞り、遺伝子変異をスクリーニングし、あわせて発見された変異チャネルの電気生理学的異常をex vivoで検証する。
さらにヒトで発見されたチャネル変異を持つてんかんモデル動物を作出し、チャネルの異常がてんかんの発症へとつながる過程を明らかにし、てんかんの分子病態をin vivoで明らかにする。

Research Products

• [Journal Article] Developmental changes in KCNQ2 and KCNQ3 expression in human brain : possible contribution to the age-dependent etiology of benign familial neonatal convulsions (2008)
  • Author(s): Kanaumi T, Takashima S, Iwasaki H, Itoh M, Mitsudome A, Hirose S.
  • Journal Title: Brain Dev 30(5) Pages: 0
  • Peer Reviewed
• [Journal Article] Progress in genetics of severe myoclonic epilepsy in fancy (2008)
  • Author(s): Kurahashi K, Wang J, Ishii A, Fukuma G, Hamachi A, Yonetani M, Ogawa A, Ohfu M, Inoue T, Yasumoto S, Hirose S.
  • Journal Title: Progress in Epileptic Disorders(In: Fukuyama Y, Takahashi T, editors. Biology of Seizere Susceptibility in Developing Brain. Paris: Editions John Libbey Eurotext Montrouge) Pages: 1-3
  • Peer Reviewed
• [Journal Article] High-Grade mature B-cell lymphoma with Burkitt-like morphology : Results of a clinicopathological study of 72 Japanese patients (2008)
  • Author(s): Nomura Y, Karube K, Suzuki R, Guo Ying, Takeshita M, Hirose S, Nakamura S, Yoshida T, Kikuchi M, Ohshima K.
  • Journal Title: Cancer Sciense 99(2) Pages: 246-52
  • Peer Reviewed
• [Journal Article] Altered KCNQ3 potassium channel function caused by the W309R pore-helix mutation found in human epilepsy (2008)
  • Author(s): Uehara A, Nakamura Y, Shioya T, Hirose S, Yasukochi M, Uehara K.
  • Journal Title: J Membr Biol 222(2) Pages: 55-63
  • Peer Reviewed
• [Journal Article] Microchromosomal deletions involving SCN1A and adjacent genes in severe myoclonic epilepsy in infancy (2008)
  • Author(s): Wang JW, Kurahashi H, Ishii A, Kojima T, Ohfu M, Inoue T, Ogawa A, Yasumoto S, Oguni H, Kure 5, Fujii T, Ito M, Okuno T, Shirasaka Y, Natsume J, Hasegawa A, Konagaya A, Kaneko S, Hirose S.
  • Journal Title: Epilepsia 49(9) Pages: 1528-34
  • Peer Reviewed
• [Journal Article] Rats Harboring S284L Chrna4 Mutation Show Attenuation of Synaptic and Extrasynaptic GABAergic Transmission and Exhibit the Nocturnal Frontal Lobe Epilepsy Phenotype (2008)
  • Author(s): Zhu G, Okada M, Yoshida S, Ueno S, Mori F, Takahara T, Saito R, Miura Y, Kishi A, Tomiyama M, Sato A, Kojima T, Fukuma G, Wakabayashi K, Hase K, Ohno H, Kijima H, Takano Y, Mitsudome A, Kaneko S, Hirose S.
  • Journal Title: J Neurosci 28(47) Pages: 12465-76
  • Peer Reviewed
• [Journal Article] Mutation screening of AP3M2 in Japanese epilepsy patients (2007)
  • Author(s): Huang MC, Okada M, Nakatsu F, Oguni H, Ito M, Morita K, Nagafuji H, Hirose S, Sakaki Y, Kaneko S, Ohno H, Kojima T.
  • Journal Title: Brain Dev 29(8) Pages: 462-7
  • Peer Reviewed
• [Journal Article] Sympathetic skin response in patients with severe motor and intellectual disabilities (2007)
  • Author(s): Ogawa A, Hamamoto K, Hirose S, Fujikawa M, Mitsudome A.
  • Journal Title: No To Hattatsu 39(5) Pages: 347-50
  • Peer Reviewed
• [Journal Article] A Type I split cord malformation is a significant pathomechanism of spina bifida aperta in neonates (2007)
  • Author(s): Ogawa A, Tomonoh Y, Hayashi H, Ohta E, R. K, Mori T, Utsunomiya H,Hirose S.
  • Journal Title: Med. Bull. Fukuoka Univ. 34(4) Pages: 261-6
  • Peer Reviewed
• [Journal Article] Midazolam for the treatment of neonatal electroencephalography-confirmed seizures (2007)
  • Author(s): Ogawa A., Shirotani G, Hashimoto J, Hayashi H, Ninomiya S, Ohta, E., Kinoshita R. M, T., Hirose S.
  • Journal Title: Med. Bull. Fukuoka Univ. 34(4) Pages: 267-71
  • Peer Reviewed
• [Journal Article] Focal epilepsy resulting from a de novo SCN1A mutation (2007)
  • Author(s): Okumura A, Kurahashi H, Hirose S, Okawa N, Watanabe K.
  • Journal Title: Neuropediatrics 38(5) Pages: 253-6
  • Peer Reviewed
• [Journal Article] Late-onset ornithine transcarbamylase deficiency in male patients : prognostic factors and characteristics of plasma amino acid profile (2006)
  • Author(s): Harada E, Nishiyori A, Tokunaga Y, Watanabe Y, Kuriya N, Kumashiro R, Kuno T, Kuromaru R, Hirose S, Ichikawa K, Yoshino M.
  • Journal Title: Pediatr Int 48(2) Pages: 105-11
  • Peer Reviewed
• [Journal Article] A new paradigm of channelopathy in epilepsy syndromes : intracellular trafficking abnormality of channel molecules (2006)
  • Author(s): Hirose S.
  • Journal Title: Epilepsy Res 70 Suppl 1 Pages: S206-17
  • Peer Reviewed
• [Journal Article] Phenotypes and genotypes in epilepsy with febrile seizures plus (2006)
  • Author(s): Ito M, Yamakawa K, Sugawara T, Hirose S,Fukuma G, Kaneko S.
  • Journal Title: Epilepsy Res 70 Suppl 1 Pages: S199-205
  • Peer Reviewed
• [Journal Article] An infant with a mitochondrial A3243G mutation demonstrating the MELAS phenotype (2006)
  • Author(s): Kanaumi T, Hirose S, Goto Y, Naitou E, Mitsudome A.
  • Journal Title: Pediatr Neurol 34(3) Pages: 235-8
• [Journal Article] Neuropathology of methylmalonic acidemia in a child (2006)
  • Author(s): Kanaumi T, Takashima S,Hirose S, Kodama T, Iwasaki H.
  • Journal Title: Pediatr Neurol 34(2) Pages: 156-9
  • Peer Reviewed
• [Journal Article] Developmental changes in the expression of GABA_A receptor alpha 1 and gamma 2 subunits in human temporal lobe, hippocampus and basal ganglia : an implication for consideration on age-related epilepsy (2006)
  • Author(s): Kanaumi T, Takashima S, Iwasaki H, Mitsudome A, Hirose S.
  • Journal Title: Epilepsy Res 71(1) : Pages: 47-53
  • Peer Reviewed
• [Journal Article] Ictal midline epileptiform discharges in benign familial neonatal convulsions (2006)
  • Author(s): Ogawa A, Hirose S, Yasumoto S, Ohfu M, Mitsudome A.
  • Journal Title: Med. Bull. Fukuoka Univ. 33(4) Pages: 305-7
  • Peer Reviewed
• [Journal Article] Involvement of Ca^<(2+)>-induced Ca^<2+> releasing system in interleukin-1β-associated adenosine release (2006)
  • Author(s): Zhu G, Okada M, Yoshida S, Mori F, Hirose S, Wakabayashi K, Kaneko S.
  • Journal Title: Eur J Pharmacol 532(3) Pages: 246-52
  • Peer Reviewed
• [Presentation] Mutational analysis for repetitive febrile seizures and sporadic febrile seizures plus in Japanese (2008)
  • Author(s): Hirose, S.
  • Organizer: 8th European Congress on Epileptology
  • Place of Presentation: Berlin
  • Year and Date: 20080918-26
• [Presentation] Benign childhood epilepsy with centrotemporal spikes following benign neonatal seizures resulting from a mutation of KCNQ2 8th European Congress on Epileptology (2008)
  • Place of Presentation: Berlin
  • Year and Date: 20080918-26
• [Presentation] The present Status and Problem of Plenatal Screening of Congenital Heart Defects ; 4 Major Refernal Centers in Kyusyu, Japan (2008)
  • Author(s): Yoshikane Y., Yoshizato T., Maeno Y., Nishibatake M., Kam N., Fusazaki N., Hirose S.
  • Organizer: The 2^<nd> Asia-Pacific Congress of Pediatrics Cordiology and Cardiac Surgery
  • Place of Presentation: Korea
  • Year and Date: 20080527-30
• [Presentation] Retrospective Analysis of Prenatally Detected Congenital Heart Defects : Six-year Experience of 4 Institutions in Japan (2008)
  • Author(s): Yashikane Y., Yoshizato T., Meno Y., Nishibatake M., Kan N., Fusazaki N.,Hirose S.
  • Organizer: 15^<th> Congress of the FAOPS
  • Place of Presentation: Nagoya
  • Year and Date: 20080520-24
• [Presentation] Study of Septicemia Due to Enterbacter Cloacae in a Tertiary Neonatal Intensive Care Unit during 1997-2007 (2008)
  • Author(s): Ohta E., Setoue T., Tsutsumi M., Inoue S., Kinoshita R., Nakamura M., Mori T., Ogawa A., Hirose S.
  • Organizer: 15^<th> Congress of the FAOPS
  • Place of Presentation: Nagoya
  • Year and Date: 20080520-24
• [Presentation] Prognoses of the Neonates of Multiple Births Admitted in NICU in recent Years (2008)
  • Author(s): Inoue T., Tsutsumi M., Kinoshita R., Ohta E., Nakamura M., Mori T., Hirose S.
  • Organizer: 15th Congress of the FAOPS
  • Place of Presentation: Nagoya
  • Year and Date: 20080520-24
• [Presentation] The Application of Genetic Tests for Epilepsy-are there Guidelines for Clinicians? (2008)
  • Author(s): Hirose S.
  • Organizer: 7^<th> Asian & Oceanian Epilepsy Congress Xiamen, China
  • Place of Presentation: Xiamen
  • Year and Date: 20080515-18
• [Presentation] Genome-Wide Identification of Febrile Seizure and Related Epilepsy Phenotype Loci (2008)
  • Author(s): Miyashita A., Kuwano R., Kojima T., Sasaki T., Zhu G, Kanai K., Fujita K., Hirose S., Kaneko S.
  • Organizer: 7^<th> Asian & Oceanian Epilepsy Congress
  • Place of Presentation: Xiamen, China
  • Year and Date: 20080515-18
• [Presentation] EEG Findings on Headache with MELAS (2008)
  • Author(s): Ihara Y., Fujita T., Inoue T., Yasumoto S., Mitsudome A., Hirose S.
  • Place of Presentation: Xiamen, China
  • Year and Date: 20080515-18
• [Presentation] Myoclonic-Astatic Epilepsy with Focal Spike Discharge may have Unfavourable Prognosis (2008)
  • Author(s): Ideguchi H., Inoue T., Ninomiya S., Fujita T., Nakamura N., Yasumoto S., Hirose S.
  • Place of Presentation: Xiamen, China
  • Year and Date: 20080515-18
• [Presentation] Non-convulsive status Lpilepticuso of Temporal Lobe Epilepsy Misdiagnosed as a Psychosomatic Disease (2008)
  • Author(s): Fujita T., Nakamura N., Inoue T., ninomiya S., Ihara Y., Tomonou Y., Ideguchi H., Yasumoto S., Mitsudome A., Hirose S.
  • Place of Presentation: Xiamen, China
  • Year and Date: 20080515-18
• [Presentation] Psychomotor Retardation Aggravated by Infantile Non-convulsive Status Epileptics in Angelman Syndrome (2008)
  • Author(s): Ninomiya S., Nakamura N., Fujita T., Ideguchi H., Inoue T., Yasumoto S., Hirose S.
  • Place of Presentation: Xiamen, China
  • Year and Date: 20080515-18
• [Presentation] A De Novo KCNQ2 Mutation Detected in Benign Neonatal Convulsions : Possible Involvement Of Genes responsible for Rare Inherited Epilepsy in Idiopathic Epilepsy (2008)
  • Author(s): Ishii A., Fukuma G., Uehara A., Yasukochi M., Miyajima T., Makita Y., Hamachi A., Yonetani M., Inoue T., Okada M., Kaneko S., Hirose S.
  • Organizer: The 4^<th> Congress of Asian Society for Pediatric Research
  • Place of Presentation: Hawaii, USA
  • Year and Date: 20080503-06
• [Presentation] Perinatal Characteristics of Early-Onset Sepsis in Neonatal Intensive Care Unit in Recent Years (2008)
  • Author(s): Tsutsumi M., Ohta E., Inoue T., Kinoshita R., Nakamura M., Mori T., Hirose S.
  • Organizer: The 4^<th> Congress of Asian Society for Pediatric Research
  • Place of Presentation: Hawaii, USA
  • Year and Date: 20080503-06
• [Presentation] Recent advances in the genetics of epilepsyJoint (2008)
  • Author(s): Hirose S.
  • Organizer: 7^<th> Human Genome Organization(HUGO)
  • Place of Presentation: 1-7cebu, Philippine
  • Year and Date: 20080400
• [Presentation] A Girl with bronchiolitis obiterans presenting recurrent lobar atelectasis (2007)
  • Author(s): Fujiwara C., Yoshikane Y., Tanaks M., Hiratsuka M., Iwasaki N., Shirakusa T., Yamaguchi S., Hiriose S.
  • Organizer: 25^<th> International Congress of Pediatrics
  • Place of Presentation: Athenes, Greece
  • Year and Date: 20070825-30
• [Presentation] Pediarictors of surgical treatment for patient ductus arteriosus in extremely low birth weight infants (2007)
  • Author(s): Yoshikane Y., Mori T., Yukitake K., Hirose S.
  • Organizer: 25^<th> International Congres of Pediatrics
  • Place of Presentation: Athenes, Greece
  • Year and Date: 20070825-30
• [Presentation] Fetal infection of Hilicobacter cinaedi manifested by fetal distress and mucous diarrhea at birth (2007)
  • Author(s): Ohta E., Fujiwara C., Mori T., Ogawa A., Adachi M., Obama H., Kawarabayashi T., Yamaguchi S.,Ono J., Hirose S.
  • Organizer: 25^<th> International Congress of Pediatrics
  • Place of Presentation: Athenes, Greece
  • Year and Date: 20070825-30
• [Presentation] Micro deletional Mutation of SCN1A in Individuals with Severe Myoclonic Epilepsy in Fancy(SMEI) and Borderline SMEI (2007)
  • Author(s): Wang J., Kurahashi K., Hamachi A., Yonetani M., Inoue T., Ogawa A., Hirose S., Yasumoto S., Kaneko S.
  • Organizer: 27^<th> International Epilepsy Congress
  • Place of Presentation: Singapole
  • Year and Date: 20070708-12
• [Presentation] Midazolam for the treatment of neonatal EEG-confirmed seizures (2007)
  • Author(s): Ogawa A., Shiratani G, Hashimoto J., Mori S., Yukitake K., Hirose S.
  • Organizer: 27^<th> International Epilepsy Congress
  • Place of Presentation: Singapore
  • Year and Date: 20070708-12
• [Patent(Industrial Property Rights)] てんかんモデル非ヒト哺乳動物 (2009)
  • Inventor(s): 廣瀬伸一
  • Industrial Property Rights Holder: (独)科学技術振興機構
  • Industrial Property Number: PCT出願,PCT/JP200*9/052230
  • Filing Date: 2009-02-10
• [Patent(Industrial Property Rights)] 変異導入遺伝子およびそれを導入したノックイン非ヒト動物 (2008)
  • Inventor(s): 廣瀬伸一
  • Industrial Property Rights Holder: (独)科学技術振興機構
  • Industrial Property Number: 特許,特願2008-273446
  • Filing Date: 2008-10-23
• [Patent(Industrial Property Rights)] てんかんモデル非ヒト哺乳動物 (2008)
  • Inventor(s): 廣瀬伸一
  • Industrial Property Rights Holder: (独)科学技術振興機構
  • Industrial Property Number: 特許,特願2008-031002
  • Filing Date: 2008-02-12