Clarification of the pathogenesis of the neurological disorders caused by impaired neuronal leucine-rich-repeat-containing transmembrane proteins.

2011 Fiscal Year Final Research Report

• Project/Area Number: 21240031
• Research Category: Grant-in-Aid for Scientific Research (A)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Neuroscience in general
• Research Institution: The Institute of Physical and Chemical Research
• Principal Investigator: ARUGA Jun 独立行政法人理化学研究所, 行動発達障害研究チーム, チームリーダー (10232076)
• Project Period (FY): 2009 – 2011
• Keywords: 比較ゲノム解析 / LRR膜タンパク質 / 疾患モデル動物 / 神経発達障害 / 精神神経疾患 / シナプス形成 / 抑制性シナプス

Research Abstract

We developed animal models for neurological disorders including autism and schizophrenia by utilizing comparative genomics. Focusing brain-enriched Leucine-rich repeat containing transmembrane proteins with unknown functions, we successfully generated new 15 strains of mouse mutants exhibiting neurological abnormalities. We collected important facts that underlie the pathogenesis of autism, schizophrenia, anxiety disorders and sensory disturbance through morphological, neurochemical, electrophysiological and pharmacological analyses.

Research Products

• [Journal Article] Selective control of inhibitory synapse development by Slitrk3-PTPdelta trans-synaptic interaction (2012)
  • Author(s): H. Takahashi, K. Katayama, K. Sohya, H. Miyamoto, T. Prasad, Y. Matsumoto, M. Ota, H. Yasuda, T. Tsumoto, J. Aruga, A. M. Craig
  • Journal Title: Nat. Neurosi
  • DOI: DOI:10.1038/nn.3040
• [Journal Article] Comparative anatomy of marmoset and mouse cortex from genomic expression (2012)
  • Author(s): H. Mashiko, A. Yoshida, S. Kikuchi, K. Niimi, E. Takahashi, J. Aruga, H. Okano, T. Shimogori
  • Journal Title: J. Neurosci Volume: 32 Pages: 5039-5053
• [Journal Article] Xenopus Zic3 controls notochord and organizer development through suppression of the Wnt/β-catenin signaling pathway (2012)
  • Author(s): T. J. Fujimi, M. Hatayama, J. Aruga
  • Journal Title: Dev. Biol Volume: 361 Pages: 220-231
• [Journal Article] GLI protein nuclear localization signal (2012)
  • Author(s): M. Hatayama, J. Aruga
  • Journal Title: Vitamins and Hormones Volume: (in press) Pages: 88
• [Journal Article] Lrrtm1と統合失調症 (2012)
  • Author(s): 佐郡和人、有賀純
  • Journal Title: 分子精神医学 Volume: 12 Pages: 47-49
• [Journal Article] LRRシナプスオーガナイザーと神経疾患 (2012)
  • Author(s): 有賀純、松本圭史
  • Journal Title: 実験医学 Volume: 30 Pages: 364-369
• [Journal Article] Impaired Cognitive Function and Altered Hippocampal Synapse Morphology in Mice Lacking Lrrtm1, a Gene Associated with Schizophrenia (2011)
  • Author(s): N. Takashima, Y. S. Odaka, K. Sakoori, T. Akagi, T. Hashikawa, N. Morimura, K. Yamada, J. Aruga
  • Journal Title: Plos One Volume: 6
• [Journal Article] A role for Zic1 and Zic2 in Myf5 regulation and somite myogenesis (2011)
  • Author(s): H. Pan, M. K. Gustafsson, J. Aruga, J. J. Tiedken, J. C. J. Chen, C. P. Emerson, Jr
  • Journal Title: Dev. Biol Volume: 351 Pages: 120-127
• [Journal Article] Impaired Auditory-Vestibular Functions and Behavioral Abnormalities of Slitrk6-Deficient Mice (2011)
  • Author(s): Y. Matsumoto, K.-i. Katayama, T. Okamoto, K. Yamada, N. Takashima, S. Nagao, J. Aruga
  • Journal Title: Plos One Volume: 6
• [Journal Article] Zic2 hypomorphic mutant mice as a schizophrenia model and ZIC2 mutations identified in schizophrenia patients (2011)
  • Author(s): M. Hatayama, A. Ishiguro, Y. Iwayama, N. Takashima, K. Sakoori, T. Toyota, Y. Nozaki, Y. S. Odaka, K. Yamada, T. Yoshikawa, J. Aruga
  • Journal Title: Scientific Reports Volume: 1
• [Journal Article] IP(3) signaling is required for cilia formation and left-right body axis determination in Xenopus embryos (2011)
  • Author(s): M. Hatayama, K. Mikoshiba, J. Aruga
  • Journal Title: Biochem. Biophys. Res. Commun Volume: 410 Pages: 520-524
• [Journal Article] Role of BMP, FGF, Calcium Signaling, and Zic Proteins in Vertebrate Neuroectodermal Differentiation (2011)
  • Author(s): J. Aruga, K. Mikoshiba
  • Journal Title: Neurochem. Res Volume: 36 Pages: 1286-1292
• [Journal Article] 統合失調症モデルとしてのZic2低発現マウスと統合失調症患者にみられるZIC2の変異 (2011)
  • Author(s): 有賀純
  • Journal Title: 分子精神医学 Volume: 11 Pages: 47-49
• [Journal Article] Slitrk1-deficient mice display elevated anxiety-like behavior and noradrenergic abnormalities (2010)
  • Author(s): K. Katayama, K. Yamada, V. G. Ornthanalai, T. Inoue, M. Ota, N. P. Murphy, J. Aruga
  • Journal Title: Mol. Psychiatry Volume: 15 Pages: 177-184
• [Journal Article] Excessive ingestion of long-chain polyunsaturated fatty acids during developmental stage causes strain-and sex-dependent eye abnormalities in mice (2010)
  • Author(s): M. Maekawa, Y. Iwayama, A. Watanabe, Y. Nozaki, T. Ohnishi, H. Ohba, M. Toyoshima, K. Hamazaki, N. Osumi, J. Aruga, T. Yoshikawa
  • Journal Title: Biochem. Biophys. Res. Commun Volume: 402 Pages: 431-437
• [Journal Article] Characterization of the tandem CWCH2 sequence motif : a hallmark of inter-zinc finger interactions (2010)
  • Author(s): M. Hatayama, J. Aruga
  • Journal Title: BMC Evol.Biol Volume: 10
• [Journal Article] Expression of ZIC family genes in meningiomas and other brain tumors (2010)
  • Author(s): J. Aruga, Y. Nozaki, M. Hatayama, Y. S. Odaka, N. Yokota
  • Journal Title: BMC Cancer Volume: 10
• [Journal Article] Stability of folding structure of Zic zinc finger proteins (2009)
  • Author(s): K. Sakai-Kato, Y. Umezawa, K. Mikoshiba, J. Aruga, N. Utsunomiya-Tate
  • Journal Title: Biochem. Biophys. Res. Commun Volume: 384 Pages: 362-365
• [Journal Article] Disorganized innervation and neuronal loss in the inner ear of Slitrk6-deficient mice (2009)
  • Author(s): K.-i. Katayama, A. Zine, M. Ota, Y. Matsumoto, T. Inoue, B. Fritzsch, J. Aruga
  • Journal Title: Plos One Volume: 4 Pages: A151-A162
• [Presentation] Characterization on Elfn family in the central nervous system (2011)
  • Author(s): Tomioka-Hara N., Yamada K., Odagawa M., Odaka Y., and Aruga J.
  • Organizer: 41st Annual Meeting of the Society for Neuroscience(Neuroscience 2011)
  • Place of Presentation: Washington DC, USA
  • Year and Date: 20111112-16
• [Presentation] Executive function deficits and altered hippocampal synapse morphology in mice lacking Lrrtm1, a gene associated with schizophrenia (2011)
  • Author(s): Aruga J., Takashima N., Odaka Y., Sakoori K., Akagi T., Hashikawa T., Morimura N., and Yamada K
  • Organizer: 41st Annual Meeting of the Society for Neuroscience(Neuroscience 2011)
  • Place of Presentation: Washington DC, USA
  • Year and Date: 20111112-16
• [Presentation] Zic2 knock down mice show the higher response to auditory stimulus and size reduction of DCoN (2011)
  • Author(s): Matsumoto Y., Takashima N., Nozaki Y., Nishioka C., Kudoh M., and Aruga J.
  • Organizer: 41st Annual Meeting of the Society for Neuroscience(Neuroscience 2011)
  • Place of Presentation: Washington DC, USA
  • Year and Date: 20111112-16
• [Presentation] Molecular and pathological characterisation of an inherited condition amongst the Amish involving high myopia and sensaorineural hearing loss (2011)
  • Author(s): Moore-Barton H., Chioza B. A., Matsumoto Y., Cross H., E., Sakoori K., Odagawa M., Gurtz K., Patton M. A., Aruga J., and Crosby A. H.
  • Organizer: British Human Genetics Conference 2011
  • Place of Presentation: Coventry, UK
  • Year and Date: 20110905-07
• [Presentation] A role of Rines, a neuronal membrane-bound ubiquitin ligase in higher brain function (2010)
  • Author(s): Kabayama-Ogawa M., Ornthanalai V., Yamada K., Murphy N. P., Katayama K., and Aruga J.
  • Organizer: 40th Annual Meeting of the Society for Neuroscience(Neuroscience 2010)
  • Place of Presentation: San Diego, USA
  • Year and Date: 20101113-17
• [Presentation] Characterisation of Slitrk2-deficient mice (2010)
  • Author(s): Corbett D. C., Katayama K., Matsumoto Y., Morimura, N., Yamada K., Ota M., Ornthanalai V., Honma C., Murphy N. P., and Aruga J.
  • Organizer: 40th Annual Meeting of the Society for Neuroscience(Neuroscience 2010)
  • Place of Presentation: San Diego, USA
  • Year and Date: 20101113-17
• [Presentation] Disorganized innervation and neuronal loss in the inner ear of Slitrk6-deficient mice (2010)
  • Author(s): Matsumoto Y., Katayama K., Zine A., Ota M., Inoue T., Fritzsch B., Yamada K., and Aruga J.
  • Organizer: 40th Annual Meeting of the Society for Neuroscience(Neuroscience 2010)
  • Place of Presentation: San Diego, USA
  • Year and Date: 20101113-17
• [Presentation] Zic2 hypomorphic mutant mice exhibit cognitive impairment and social behavior abnormalities with an altered distribution of basal forebrain cholinergic neurons (2010)
  • Author(s): Aruga J., Hatayama M., Takashima N., Sakoori K., Nozaki Y., Odaka Y., Yamada K., and Ishiguro A
  • Organizer: 40th Annual Meeting of the Society for Neuroscience(Neuroscience 2010)
  • Place of Presentation: San Diego, USA
  • Year and Date: 20101113-17
• [Remarks] 機関および研究室ホームページでの研究成果紹介
  • URL: http://www.riken.jp/r-world/info/release/press/2012/120130/index.html
• [Remarks]
  • URL: http://lcn.brain.riken.jp/Slitrk3_inhibitorysynapse.html
• [Remarks]
  • URL: http://lcn.brain.riken.jp/Takashima_Lrrtm1.html
• [Remarks]
  • URL: http://lcn.brain.riken.jp/Hatayama_Zic2_SCZ_2011.html
• [Remarks]
  • URL: http://lcn.brain.riken.jp/Matsumoto_Slitrk6_vestibular_function.html