Molecular basis for the complex neurocristopathy PCWH and mechanisms underlying SOX10 allelic affinity

• Project/Area Number: 21390103
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Human genetics
• Research Institution: National Center of Neurology and Psychiatry
• Principal Investigator: INOUE Ken 独立行政法人国立精神・神経医療研究センター, 神経研究所疾病研究第二部, 室長 (30392418)
• Co-Investigator(Kenkyū-buntansha): INOUE Takayoshi 独立行政法人国立精神・神経医療研究センター, 神経研究所病態生化学研究部, 室長 (20370984) ; DEGUCHI Kimiko 独立行政法人国立精神・神経医療研究センター, 神経研究所疾病研究第二部, 研究生 (50227542)
• Project Period (FY): 2009 – 2011
• Project Status: Completed (Fiscal Year 2011)
• Budget Amount: ¥18,720,000 (Direct Cost: ¥14,400,000、Indirect Cost: ¥4,320,000); Fiscal Year 2011: ¥5,980,000 (Direct Cost: ¥4,600,000、Indirect Cost: ¥1,380,000); Fiscal Year 2010: ¥5,980,000 (Direct Cost: ¥4,600,000、Indirect Cost: ¥1,380,000); Fiscal Year 2009: ¥6,760,000 (Direct Cost: ¥5,200,000、Indirect Cost: ¥1,560,000)
• Keywords: 分子遺伝学 / BACトランスジェニックマウス / 神経科学 / 脳神経疾患 / 遺伝学 / 発生・分化

Research Abstract

SOX10 mutations cause either Waardenburg-Hirshcsprung disease(WS4) or Peripheral demyelinating neuropathy, Central dysmyelinating leukodystrophy, Waardenburg syndrome, and Hirshcsprung disease(PCWH). We have been studying the molecular mechanisms underlying allelic affinity observed in SOX10 mutations by in vitro analyses. In this proposal, we sought to determine the cellular pathology of PCWH using BAC transgenic mice and to clarify the molecular basis for the allelic affinity in vivo.

Research Products

• [Journal Article] Brain N-acetylaspartate is increased in mice with hypomyelination (2012)
  • Author(s): Takanashi J, Saito S, Aoki I, Barkovich J, Itoh Y, Inoue K.
  • Journal Title: J Magn Reson Imaging Volume: 35 Issue: 2 Pages: 418-425
  • DOI: 10.1002/jmri.22817
  • Peer Reviewed
• [Journal Article] Effect of curcumin in a mouse model of Pelizaeus-Merzbacher disease (2012)
  • Author(s): Yu L-H, Morimura T, Numata Y, Yamamoto R, Inoue N, Antalfy B, Goto Y, Deguchi K, Osaka H, Inoue K.
  • Journal Title: Mol Genet Metab Volume: 106 Issue: 1 Pages: 108-114
  • DOI: 10.1016/j.ymgme.2012.02.016
  • Peer Reviewed
• [Journal Article] Genome-wide association study identifies HLA-DP as a susceptibility gene for pediatric asthma in Asian populations (2011)
  • Author(s): Noguchi E, Sakamoto H, Hirota T, Ochiai K, Imoto Y, Sakashita M, Kurosaka F, Akasawa A, Yoshihara S, Kanno N, Yamada Y, Shimojo N, Kohno Y, Suzuki Y, Kang MJ, Kwon JW, Hong SJ, Inoue K, Goto Y, Yamashita F, Asada T, Hirose H, Saito I, Fujieda S, Hizawa N, Sakamoto T, Masuko H, Nakamura Y, Nomura I, Tamari M, Arinami T, Yoshida T, Saito H, Matsumoto K
  • Journal Title: PLoS Genet Volume: 7(7) Issue: 7 Pages: 1002170-1002170
  • DOI: 10.1371/journal.pgen.1002170
  • Peer Reviewed
• [Journal Article] Mutations in POLR3A and POLR3B encoding RNA Polymerase III subunits cause an autosomal-recessive hypomyelinating leukoencephalopathy. (2011)
  • Author(s): Saitsu H. et al.
  • Journal Title: Am J Hum Genet. Volume: 89 Issue: 5 Pages: 644-651
  • DOI: 10.1016/j.ajhg.2011.10.003
  • Peer Reviewed
• [Journal Article] Genome-wide association study identifies HLA-DP as a susceptibility gene for pediatric asthma in Asian populations (2011)
  • Author(s): Noguchi E, 他33名
  • Journal Title: PLoS Genet Volume: 7 Issue: 7 Pages: e1002171-e1002171
  • DOI: 10.1371/journal.pgen.1002171
  • Peer Reviewed
• [Journal Article] 先天性大脳白質形成不全症:Pelizaeus-Merzbacher病とその類縁疾患 (2011)
  • Author(s): 井上健, 他6名
  • Journal Title: 脳と発達(総説) Volume: 43 Pages: 435-442
  • NAID: 10030290993
  • Peer Reviewed
• [Journal Article] Bacterial artificial chromosomes as analytical basis for gene transcriptional machineries (2011)
  • Author(s): Asami J, 他4名
  • Journal Title: Transgenic Research誌 Volume: 20 Issue: 4 Pages: 913-924
  • DOI: 10.1007/s11248-010-9469-3
  • Peer Reviewed
• [Journal Article] Disrupted SOX10 regulation of GJC2 transcription causes Pelizaeus-Merzbacher-like disease (2010)
  • Author(s): Osaka H, Hamanoue H, Yamamoto R, Nezu A, Sasaki M, Saitsu H, Kurosawa K, Shimbo H, Matsumoto N, Inoue K.
  • Journal Title: Ann Neurol Volume: 68 Issue: 2 Pages: 250-4
  • DOI: 10.1002/ana.22022
  • Peer Reviewed
• [Journal Article] Abnormal enteric innervation identified without histopathologic staining in aganglionic colorectum from a mouse model of Hirschsprung's disease (2010)
  • Author(s): Miyahara K, Kato Y, Koga H, Lane G J, Inoue T, Akazawa C, Yamataka A.
  • Journal Title: J Pediatr Surg Volume: 45 Issue: 12 Pages: 2403-2407
  • DOI: 10.1016/j.jpedsurg.2010.08.039
  • Peer Reviewed
• [Journal Article] Low copy repeatとゲノム病遺伝子診療学 (2010)
  • Author(s): 井上健
  • Journal Title: 日本臨床 Volume: 68増刊号8 Pages: 80-86
  • URL: http://www.nippon-rinsho.co.jp/backnum/z_mokuji/6808idensi.html
• [Journal Article] Sox10-Venus mice : a new tool for real-time labeling of neural crest lineage cells and oligodendrocytes (2010)
  • Author(s): Shibata S, Yasuda A, Renault-Mihara F, Suyama S, Katoh H, Inoue T, Inoue, YU, Nagoshi N, Sato M, Nakamura M, Akazawa C, Okano H.
  • Journal Title: Mol Brain Volume: 3 Issue: 1 Pages: 31-31
  • DOI: 10.1186/1756-6606-3-31
  • Peer Reviewed
• [Journal Article] Disrupted SOX10 regulation of GJC2 transcription causes Pelizaeus-Merzbacher-like disease (2010)
  • Author(s): Osaka H, Hamanoue H, Yamamoto R, Nezu A, Sasaki M, Saitsu H, Kurosawa K, Shimbo H, Matsumoto N, Inoue K
  • Journal Title: Annals of Neurology Volume: 68(2) Pages: 250-254
  • Peer Reviewed
• [Journal Article] Low copy repeatとゲノム病 (2010)
  • Author(s): 井上健
  • Journal Title: 日本臨床 Volume: 68増刊号8 Pages: 80-86
• [Journal Article] Sox10-Venus mice : a new tool for real-time labeling of neural crest lineage cells and oligodendrocytes (2010)
  • Author(s): Shibata S, Yasuda A, Renault-Mihara F, Suyama S, Katoh H, Inoue T, Inoue, YU, Nagoshi N, Sato M, Nakamura M, Akazawa C, Okano H
  • Journal Title: Mol.Brain Volume: 3 Pages: 31-31
  • Peer Reviewed
• [Journal Article] Pelizaeus-Merzbacher病-Double, Double and Trouble2009小児科 (2009)
  • Author(s): 井上健,小坂仁
  • Journal Title: 小児疾患における臨床遺伝学の進歩 Volume: 50(7)増刊号 Pages: 881-887
• [Journal Article] Pelizaeus-Merzbacher病-Double, Double…and Trouble- (2009)
  • Author(s): 井上健, 小坂仁
  • Journal Title: 小児科 Volume: 50 Pages: 881-887
• [Presentation] 先天性大脳白質形成不全症の統合的研究の推進 (2011)
  • Author(s): 井上健、岩城明子、黒澤健司、高梨潤一、出口貴美子、山本俊至、小坂仁
  • Organizer: 第56回日本人類遺伝学会総会
  • Place of Presentation: 千葉
  • Year and Date: 2011-11-12
• [Presentation] 先天性大脳白質形成不全症の統合的研究の推進 (2011)
  • Author(s): 井上健, 他
  • Organizer: 第56回日本人類遺伝学会総会
  • Place of Presentation: 千葉、幕張メッセ
  • Year and Date: 2011-11-12
• [Presentation] Pelizaeus-Merzbacherlike-diseaseにおけるGJC2プロモーター変異の分子病態解析 (2011)
  • Author(s): 後藤玲央、小坂仁、新保裕子、後藤雄一、井上健
  • Organizer: 第56回日本人類遺伝学会総会
  • Place of Presentation: 千葉
  • Year and Date: 2011-11-10
• [Presentation] Pelizaeus-Merzbacher-like-diseaseにおけるGJC2プロモーター変異の分子病態解析 (2011)
  • Author(s): 後藤玲央, 他
  • Organizer: 第56回日本人類遺伝学会総会
  • Place of Presentation: 千葉、幕張メッセ
  • Year and Date: 2011-11-10
• [Presentation] A comprehensive nation-wide epidemiological survey for Pelizaeus-Merzbacher disease and associated disorders in Japan (2011)
  • Author(s): Inoue K, Numata Y, Ohkubo T, Arima E, Iwaki A, Kurosawa K, Takanashi J, Deguchi K, Yamamoto T, Osaka H.
  • Organizer: 12^<th> International Congress of Human Genetics
  • Place of Presentation: Montreal, Canada
  • Year and Date: 2011-10-13
• [Presentation] A comprehensive nation-wide epidemiological survey for Pelizaeus-Merzbacher disease and associated disorders in Japan (2011)
  • Author(s): Inoue K, et al
  • Organizer: 12^<th> International Congress of Human Genetics
  • Place of Presentation: Montreal Convention Centre, Montreal, Canada
  • Year and Date: 2011-10-13
• [Presentation] 先天性大脳白質形成不全症の診断基準と疾患分類の作成 (2011)
  • Author(s): 井上健,岩城明子,黒澤健司,高梨潤一,出口貴美子,山本俊至,小坂仁
  • Organizer: 第53回日本小児神経学会
  • Place of Presentation: 横浜
  • Year and Date: 2011-05-26
• [Presentation] A SOX10 binding site mutation in GJC2 promoter causes Pelizaeus-Merzbacher-like disease (2011)
  • Author(s): Osaka H, Nezu A, Saitsu H, Kurosawa K, Matsumoto N, Inoue K.
  • Organizer: 第53回日本小児神経学会
  • Place of Presentation: 横浜
  • Year and Date: 2011-05-26
• [Presentation] 先天性大脳白質形成不全症の診断基準と疾患分類の作成 (2011)
  • Author(s): 井上健, 他
  • Organizer: 第53回日本小児神経学会
  • Place of Presentation: 横浜、パシフィコ横浜
  • Year and Date: 2011-05-26
• [Presentation] A SOX10 binding site mutation in GJC2 promoter causes Pelizaeus-Merzbacher-like disease (2011)
  • Author(s): Osaka H, 他
  • Organizer: 第53回日本小児神経学会
  • Place of Presentation: 横浜、パシフィコ横浜
  • Year and Date: 2011-05-26
• [Presentation] Sox10 BAC transgenic mouse modeling a complex neurocristopathy, PCWH (2010)
  • Author(s): K. Inoue, N. Aoyagi-Inoue, Y. Itoh, Y. Inoue Y. Matsuda, M. Inagaki, T. Inoue, Y. Goto, S. Kohsaka, C. Akazawa
  • Organizer: 60^<th> Annual meeting of the American Society of Human Genetics
  • Place of Presentation: Washington DC, USA
  • Year and Date: 2010-11-04
• [Presentation] Sox10 BAC transgenic mouse modeling a complex neurocristopathy, PCWH (2010)
  • Author(s): Inoue K, Aoyagi-Inoue N, Itoh Y, Inoue Y, Matsuda Y, Inagaki M, Inoue T, Goto Y, Kohsaka S, Akazawa C
  • Organizer: 60^<th> Annual meeting of the American Society of Human Genetics
  • Place of Presentation: Washington Convention Center, Washington DC, USA
  • Year and Date: 2010-11-04
• [Presentation] 変異型Sox10BACトランスジェニックマウスによる複合型神経堤症候群PCWHのモデル動物の作成 (2010)
  • Author(s): 伊藤亨子、井上直子、井上由紀子、松田芳樹、稲垣真澄、高坂新一、後藤雄一、井上高良、赤澤智宏、井上健
  • Organizer: 第55回日本人類遺伝学会総会
  • Place of Presentation: 大宮
  • Year and Date: 2010-10-30
• [Presentation] 変異型Sox10BACトランスジェニックマウスによる複合型神経堤症候群PCWHのモデル動物の作成 (2010)
  • Author(s): 伊藤亨子、井上直子、井上由紀子、松田芳樹、稲垣真澄、高坂新一、後藤雄一、井上高良、赤澤智宏、井上健
  • Organizer: 第55回日本人類遺伝学会総会
  • Place of Presentation: 大宮ソニックシティ、大宮
  • Year and Date: 2010-10-30
• [Presentation] Modeling a complex neurocristopathy, PCWH, in a Sox10 BAC transgenic mouse (2010)
  • Author(s): K Inoue, N Aoyagi-Inoue, Y Itoh, Y Inoue, Y Matsuda, M Inagaki, T Inoue, Y Goto, S Kohsaka, C Akazawa
  • Organizer: 18th Biennial Meeting of the International Society for Development Neuroscience
  • Place of Presentation: Estoril, Portugal
  • Year and Date: 2010-06-08
• [Presentation] Abnormal neuronal migration with ischemic brain injuries may cause cognitive dysfunction in extremely preterm infants (2010)
  • Author(s): K Deguchi, K Kubo, DL Armstrong, K Nakajima, K Inoue
  • Organizer: 18th Biennial Meeting of the International Society for Development Neuroscience
  • Place of Presentation: Estoril, Portugal
  • Year and Date: 2010-06-08
• [Presentation] Modeling a complex neurocristopathy, PCWH, in a Sox10 BAC transgenic mouse (2010)
  • Author(s): Inoue K, Aoyagi-Inoue N, Itoh Y, Inoue Y, Matsuda Y, Inagaki M, Inoue T, Goto Y, Kohsaka S, Akazawa C
  • Organizer: 18th Biennial Meeting of the International Society for Development Neuroscience
  • Place of Presentation: Estoril Convention Centre, Estoril, Portugal
  • Year and Date: 2010-06-08
• [Presentation] Abnormal neuronal migration with ischemic brain injuries may cause cognitive dysfunction in extremely preterm infants (2010)
  • Author(s): Deguchi K, Kubo K, Armstrong DL, Nakajima K, Inoue K
  • Organizer: 18th Biennial Meeting of the International Society for Development Neuroscience
  • Place of Presentation: Estoril Convention Centre, Estoril, Portugal
  • Year and Date: 2010-06-08
• [Presentation] Curcumin partially mitigated the phenotype of Pelizaeus-Merzbacher disease caused by PLP1 point mutations in mouse (2009)
  • Author(s): K. Inoue, L-H. Yu, T. Morimura, H. Iwashita, R. Yamamoto, K. Deguchi, B. Antalfy, N. Inoue, H. Osaka, M. Itoh, Y. Goto
  • Organizer: 59^<th> Annual meeting of the American Society of Human Genetics
  • Place of Presentation: Honolulu, HI
  • Year and Date: 2009-10-23
• [Presentation] Curcumin partially mitigated the phenotype of Pelizaeus-Merzbacher disease caused by PLP1 point mutation in mouse (2009)
  • Author(s): Inoue K, et al.
  • Organizer: 59^<th> Annual meeting of American Society of Human Genetics
  • Place of Presentation: 米国 ハワイHawaii Convention Center
  • Year and Date: 2009-10-23
• [Presentation] Pelizaeus-Merzbacher病の遺伝カウンセリング (2009)
  • Author(s): 西川智子、松浦公美、古旗美恵子、橋本啓典、古谷憲孝、小坂仁、井上健、黒澤健司
  • Organizer: 第54回日本人類遺伝学会総会
  • Place of Presentation: 品川
  • Year and Date: 2009-09-25
• [Presentation] 先天性大脳白質形成不全症の全国疫学調査および遺伝子解析研究の推進について (2009)
  • Author(s): 井上健、小坂仁、黒澤健司、高梨潤一、山本俊至、岩城明子
  • Organizer: 第54回日本人類遺伝学会総会
  • Place of Presentation: 品川
  • Year and Date: 2009-09-24
• [Presentation] 先天性大脳白質形成不全症の全国疫学調査および遺伝子解析研究の推進について (2009)
  • Author(s): 井上健, 他
  • Organizer: 第54回日本人類遺伝学会
  • Place of Presentation: 東京 グランドプリンスホテル高輪
  • Year and Date: 2009-09-24
• [Presentation] 変異Sox10トランスジェニックマウスを用いた複合型神経堤症候群PCWHの病態解析 (2009)
  • Author(s): 井上直子、井上由紀子、松田芳樹、稲垣真澄、井上高良、後藤雄一、高坂新一、井上健、赤澤智宏
  • Organizer: 第34回日本神経科学大会
  • Place of Presentation: 名古屋
  • Year and Date: 2009-09-17
• [Presentation] 変異Sox10トランスジェニックマウスを用いた複合型神経堤症候群PCWHの病態解析 (2009)
  • Author(s): 井上直子, 他
  • Organizer: 第32回日本神経科学大会
  • Place of Presentation: 名古屋 名古屋国際会議場
  • Year and Date: 2009-09-17
• [Book] Bacterial Artificial Chromosome-Based Experimental Strategies in the Field of Developmental Neuroscience. In : Bacterial Artificial Chromosomes Edited by P Chatterjee (2011)
  • Author(s): Y Terakawa, YU. Inoue, J Asami, T Inoue
  • Publisher: InTech
• [Book] Bacterial Artificial Chromosomes (Chapter 7 ; pp103-118) (2011)
  • Author(s): Terakawa YW, 他3名
  • Total Pages: 136
  • Publisher: InTech
• [Patent(Industrial Property Rights)] トランスジェニック非ヒト動物 (2009)
  • Inventor(s): 赤澤智宏、井上高良、井上健、高坂新一
  • Industrial Property Rights Holder: 赤澤智宏、井上高良、井上健、高坂新一
  • Industrial Property Number: 2009-001082
  • Filing Date: 2009-01-06