The functional analysis of !6q-linled autosomal dominant cerabeller ataxia associated gene.

• Project/Area Number: 17590866
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Neurology
• Research Institution: Tokyo Medical and Dental University
• Principal Investigator: TORU Shuta Tokyo Medical and Dental University, Neurology, Part-time Lecturer, 医学部, 非常勤講師 (50376711)
• Co-Investigator(Kenkyū-buntansha): ISHIKAWA Kinya Tokyo Medical and Dental University, Neurology, Lecturer, 医学部附属病院, 講師 (30313240)
• Project Period (FY): 2005 – 2006
• Project Status: Completed (Fiscal Year 2006)
• Budget Amount: ¥3,500,000 (Direct Cost: ¥3,500,000); Fiscal Year 2006: ¥1,700,000 (Direct Cost: ¥1,700,000); Fiscal Year 2005: ¥1,800,000 (Direct Cost: ¥1,800,000)
• Keywords: Central nervous system disease / Neuroscience / Spinocerebeller ataxia / 第16番染色体長腕 / 優性遺伝性小脳変性症 / puratrophin-1 / two-hybrid system法 / 細胞骨格蛋白 / 16q-ADCA typeIII / 原因遺伝子

Research Abstract

A purpose of this study is to analyze it about an associated gene of prepotence to chain the 16th chromosome length arm-related cerebellum transsexualism. As for this disease, we performed identification of a cause gene seat, manufacture of physical map, limitation of a candidate domain till now. Furthermore, in a puratrophin-1 gene, chain reaction non-equilibrium found a high change. When we made an antibody for puratrophin-1 and analyzed it in a patient brain immunohistochemically, the protein cohered with cytoskeletal protein with a patient cerebellum Purkinje cell. It is a gene change or this is an only change peculiar to a patient, and it is a direct cause of the onset of this disease or it was related to extremely closely.
From a background such as the above, we inspected it whether this change was etiology. We used two-hybrid system method from a library and did cloning of cDNA of the protein which formed interaction or a complex to this protein to examine a characteristic of a product of a puratrophin-1 gene. We built puratrophin-1 and yeast transcription gene bait plasmid to include and introduced it into host yeast together when I tied the Homo sapiens fetus brain cDNA library which became an object of screening to a transcription activation domain of a yeast transcription factor and produced it. We did screening of the positive colony which we grew on a nutrient medium and collected plasmid DNA from a yeast cell to hold a positive clone in. Base sequence parses this by a direct sequence method and identifies protein, but a thing related to cytoskeletal protein does not become clear. We are examining including manufacture of a polyclonal antibody, in situ hybridization now. There may be a cause gene of this disease elsewhere and examines a candidate domain in detail and is contributing it about the result.

Research Products

• [Journal Article] On autosomal dominant cerebellar ataxia (ADCA) other than polyglutamine diseases, with special reference to chromosome 16q22.1-linked ADCA. (2006)
  • Author(s): Ishikawa K, Mizusawa H
  • Journal Title: Neuropathology 26(4) Pages: 352-360
  • NAID: 10018059239
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] 16q-linked autosomal dominant cerebellar ataxia : a clinical and genetic study (2006)
  • Author(s): Ouyang Y, Sakoe K, Shimazaki H, Namekawa M, Ogawa T, Ando Y, Kawakami T, Kaneko J, Hasegawa Y, Yoshizawa K, Amino T, Ishikawa K, et al.
  • Journal Title: J Neurol Sci 247(2) Pages: 180-186
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] A -16C>T substitution in the 5' UTR of the puratrophin-1 gene is prevalent in autosomal dominant cerebellar ataxia in Nagano. (2006)
  • Author(s): Ohata T, Yoshida K, Sakai H, Hamanoue H, Mizuguchi T, Shimizu Y, Okano T, Takada F, Ishikawa K, et al.
  • Journal Title: J Hum Genet 51(5) Pages: 461-466
  • NAID: 10019168027
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] On autosomal dominant cerebellar ataxia (ADCA) other than polyglutamine diseases, with special reference to chromosome 16q22.1-linked ADCA. (2006)
  • Author(s): Ishikawa K, Mizusawa H.
  • Journal Title: Neuropathology 26(4) Pages: 352-360
  • NAID: 10018059239
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] A -16C>T substitution in the 5'UTR of the puratrophin-1 gene is prevalent is autosomal dominant cerebellar ataxia in Nagano. (2006)
  • Author(s): Ohata T, Yoshida K, Sakai H, Hamanoue H, Mizuguchi T, Shimizu Y, Okano T, Takada F, Ishikawa K, et al.
  • Journal Title: J Hum Genet 51(5) Pages: 461-466
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] An autosomal dominant cerebellar ataxia linked to chromosome 16q22.1 is associated with a single-nucleotide substitution in the 5' untranslated region of the gene encoding a protein with spectrin repeat and Rho guanine-nucleotide exchange-factor domains. (2006)
  • Author(s): Ishikawa K, Toru S, Tsunemi T, Li M, Kobayashi K, Yokota T, Amino T, et al.
  • Journal Title: Am J Hum Genet 77(2) Pages: 280-296
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] 脊髄小脳萎縮症の新しい病型と病態 (2006)
  • Author(s): 融 衆太, 水澤英洋
  • Journal Title: Annual Review神経 2007 Pages: 183-193
• [Journal Article] 【脊髄小脳変性症研究の最近の進歩】 常染色体優性遺伝性脊髄小脳変性症 第16番染色体長腕に連鎖する優性遺伝性脊髄小脳変性症 (2006)
  • Author(s): 石川欽也, 融 衆太, 水澤英洋
  • Journal Title: 神経研究の進歩 50巻3号 Pages: 355-362
• [Journal Article] On autosomal dominant cerebellar ataxia (ADCA) other than polyglutamine diseases with special reference to chromosome 16q22. 1-linked ADCA. (2006)
  • Author(s): Ishikawa K., Mizusawa H.
  • Journal Title: Neuropathology 26(4) Pages: 352-360
• [Journal Article] 16q-linked autosomal dominant cerebellar ataxia : a clinical and genetic study. (2006)
  • Author(s): Ouyang Y, Sakoe K, Shimazaki H, Namekawa M, Ogawa T, Ando Y, Kawakami T, Kaneko J, Hasegawa Y, Yoshizawa K, Amino T, Ishikawa K, Mizusawa H, Nakano I, Takiyama Y.
  • Journal Title: J Neurol Sci. 247(2) Pages: 180-186
• [Journal Article] A -16C>T substitution in the 5' UTR of the puratrophin-1 gene is prevalent in autosomal dominant cerebellar ataxia in Nagano. (2006)
  • Author(s): Ohata T, Yoshida K, Sakai H, Hamanoue H, Mizuguchi T, Shimizu Y, Okano T, Takada F, Ishikawa K, Mizusawa H, Yoshiura K, Fukushima Y, Ikeda S, Matsumoto N.
  • Journal Title: Journal of Human Genetics 51(5) Pages: 461-466
  • NAID: 10019168027
• [Journal Article] A clinical, genetic, and neuropathologic study in a family with 16q-linked ADCA type III. (2005)
  • Author(s): Owada K, Ishikawa K, Toru S, Ishida G, et al.
  • Journal Title: Neurology 65(4) Pages: 629-632
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] An autosomal dominant cerebellar ataxia linked to chromosome 16q22.1 is associated with a single-nucleotide substitution in the 5' untranslated region of the gene encoding a protein with spectrin repeat and Rho guanine-nucleotide exchange-factor domains. (2005)
  • Author(s): Ishikawa K, Toru S, Tsunemi T, Li M, Kobayashi K, Yokota T, Amino T, Owada K, et al.
  • Journal Title: Am J Hum Genet 77(2) Pages: 280-296
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Somatosensory-evoked cortical potential during attacks of paroxysmal dysesthesia in multiple sclerosis. (2005)
  • Author(s): Toru S, Yokota T, Tomimitsu H, et al.
  • Journal Title: Eur J Neurol 12(3) Pages: 233-234
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] A clinical, genetic, and neuropathologic study in a family with 16q-linked ADCA type III (2005)
  • Author(s): Owada K, Ishikawa K, Toru S, Ishida G, et al.
  • Journal Title: Neurology 65(4) Pages: 629-632
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] A clinical, genetic, and neuropathologic study in a family with 16q-linked ADCA typeIII. (2005)
  • Author(s): Owada K, Ishikawa K, Toru S, Ishida G, Gomyoda M, Tao O, Noguchi Y, Kitayama K, Kondo I, Noguchi E, Arinami T, Mizusawa H.
  • Journal Title: Neurology 65(4) Pages: 629-632
• [Journal Article] An autosomal dominant cerebellar ataxia linked to chromosome 16q22.1 is associated with a single-nucleotidesubstitution in the 5 untranslated region of the gene encoding a protein with spectrin repeat and Rho guanine-nucleotide exchange-factor domains. (2005)
  • Author(s): Ishikawa K, Toru S, Tsunemi T, Li M, Kobayashi K, Yokota T, Amino T, Owada K, Fujigasaki H, Sakamoto M, Tomimitsu H, Takashima M, Kumagai J, Noguchi Y, Kawashima Y, Ohkoshi N, Ishida G, Gomyoda M, Yoshida M, Hashizume Y, Saito Y, Murayama S, Yamanouchi H, Mizutani T, Kondo I, Toda T, Mizusawa H.
  • Journal Title: Am J Hum Genet. 77(2) Pages: 280-296
• [Journal Article] Somatosensory-evoked cortical potential during attacks of paroxysmal dysesthesia in multiple sclerosis. (2005)
  • Author(s): Toru S, Yokota T, Tomimitsu H, Kanouchi T, Yamada M, Mizusawa H.
  • Journal Title: Eur J Neurol. 12(3) Pages: 233-234