VPS13A遺伝子が関連する新たな神経細胞死カスケードの解明

• Project/Area Number: 18023029
• Research Category: Grant-in-Aid for Scientific Research on Priority Areas
• Allocation Type: Single-year Grants
• Review Section: Biological Sciences
• Research Institution: Kagoshima University
• Principal Investigator: 佐野 輝 Kagoshima University, 大学院・医歯学総合研究科, 教授 (30178800)
• Co-Investigator(Kenkyū-buntansha): 中村 雅之 鹿児島大学, 医学部・歯学部附属病院, 助教 (90332832)
• Project Period (FY): 2006 – 2007
• Project Status: Completed (Fiscal Year 2007)
• Budget Amount: ¥7,900,000 (Direct Cost: ¥7,900,000); Fiscal Year 2007: ¥3,600,000 (Direct Cost: ¥3,600,000); Fiscal Year 2006: ¥4,300,000 (Direct Cost: ¥4,300,000)
• Keywords: chorea acanthocytosis / chorein / VPS13A / major depressive disorder / vascular endothelial growth factor / brain-derived neurotrophic factor / schizophrenia / NDE1 / 有棘赤血球舞踏病 / VPS13A遺伝子 / 神経細胞死 / 神経変性 / Gephyrin / GABA-A受容体

Research Abstract

有棘赤血球舞踏病(Chorea-acanthosis; ChAc)の臨床から分子的研究を精力的に進めており、発表業績につながっている。臨床的には、ChAcの大家系例でヘテロ接合性の保因者に部分症候が出現することを発見し(J Neurol Sci 263,124-132,2007)、またChAcに心筋症の合併症例を見出した(Mov Disord 22,1669-1670,2007)。ChAc病因遺伝子VPS13Aの産物choreinに対する特異抗体の作成によって、免疫組織化学的に組織分布を検討し(Biochem Biophys Res Commun 353,431-435,2007)、脳特異的mRNAバリアントを発見した(Biochem Biophys Res Commun 353,902-907,2007)。
機能性精神疾患の分子遺伝学研究としては、うつ病のvascular endothelial growth factor遺伝子多型との関連や(Prog Neuropsychopharmacol Biol Psychiatry 31,658-63,2007)、brain-derived neurotrophic factor遺伝子多型との関連(Am J Med Genet B Neuropsychiatr Genet 144,1003-1006)、また統合失調症でのNDE1遺伝子多型との非関連性を明らかにした(Schizophr Res 99,367-9,2007)。

Research Products

• [Journal Article] In vivo distribution and localization of chorein. (2007)
  • Author(s): Kurano Y, Nakamura M, Ichiba M, Matsuda M, Mizuno E, Kato M, Agemura A, Izumo S and Sano A
  • Journal Title: Biochem Biophys Res Commun 353 Pages: 431-5
  • Peer Reviewed
• [Journal Article] Neurologic phenotypes associated with acanthocytosis. (2007)
  • Author(s): Walker RH, Jung HH, Dobson-Stone C, Rampoldi L, Sano A, Tison F and Danek A
  • Journal Title: Neurology 68 Pages: 92-8
  • Peer Reviewed
• [Journal Article] Brain-specific transcript variants of 5' and 3' ends of mouse VPS13A and VPS13C. (2007)
  • Author(s): Mizuno E, Nakamura M, Agemura A, Kusumoto A, Ichiba M, Kurano Y, Muroya S and Sano A
  • Journal Title: Biochem Biophys Res Commun 353 Pages: 902-7
  • Peer Reviewed
• [Journal Article] Gene expression and association analysis of vascular endothelialgrowth factor in major depressive disorder. (2007)
  • Author(s): Iga J, Ueno S, Yamauchi K, Numata S, Tayoshi-Shibuya S, Kinouchi S, Nakataki M, Song H, Hokoishi K, Tanabe H, Sano A and Ohmori T
  • Journal Title: Prog Neuropsychopharmacol Biol Psychiatry 31 Pages: 658-63
  • Peer Reviewed
• [Journal Article] Differences in two mice strains on kainic acid-induced amygdalar seizures. (2007)
  • Author(s): Kasugai M, Akaike K, Imamura S, Matsukubo H, Tojo H, Nakamura M, Tanaka S and Sano A
  • Journal Title: Biochem Biophys Res Commun 357 Pages: 1078-83
  • Peer Reviewed
• [Journal Article] A new phenotype of chorea-acanthocytosis with dilated cardiomyopathy and myopathy. (2007)
  • Author(s): Kageyama Y, Matsumoto K, Ichikawa K, Ueno SI, Ichiba M, Nakamura M and Sano A
  • Journal Title: Mov Disord 22 Pages: 1669-1670
  • Peer Reviewed
• [Journal Article] Distribution of prosaposin in the rat nervous system. (2007)
  • Author(s): Hosoda Y, Miyawaki K, Saito S, Chen J, Bing X, Terashita T, Kobayashi N, Araki N, Shimokawa T, Hamada F, Sano A, Tanabe H, Matsuda S
  • Journal Title: Cell Tissue Res 330 Pages: 197-207
  • Peer Reviewed
• [Journal Article] Clinical and molecular genetical assessment of a chorea-acanthocytosis pedigree. (2007)
  • Author(s): Ichiba M, Nakamura M, Kusumoto A, Mizuno E, Kurano Y, Matsuda M, Kato M, Tomemori Y, Muroya S, Nakabepu Y, Sano A
  • Journal Title: J Neurol Sci 263 Pages: 124-132
  • Peer Reviewed
• [Journal Article] The Val66Met polymorphism of the brain-derived neurotrophic factor gene is associated with psychotic feature and suicidal behavior in Japanese major depressive patients. (2007)
  • Author(s): Iga JI, Ueno SI, Yamauchi K, Numata S, Tayoshi-Shibuya S, Kinouchi S, Nakataki M, Song H, Hokoishi K, Tanabe H, Sano A and Ohmori T:
  • Journal Title: Am J Med Genet B Neuropsychiatr Genet 144 Pages: 1003-6
  • Peer Reviewed
• [Journal Article] Expression patterns in alternative splicing forms of prosaposinmRNA in the rat facial nerve nucleus after facial nerve transection (2007)
  • Author(s): Chen J, Saito S, Kobayashi N, Sato K, Terashita T, Shimokawa T, Mominoki K, Miyawaki K, Sano A, Matsuda S
  • Journal Title: Neurosci Res 60 Pages: 82-94
  • Peer Reviewed
• [Journal Article] No association between the NDE1 gene and schizophrenia in the Japanese Population. (2007)
  • Author(s): Numata N, Ueno S, Iga J, Nakataki M, Tanahashi T, Itakura M, Sano A, Ohi K, Hashimoto R, Takeda M, Ohmori T
  • Journal Title: Schizophr Res 99 Pages: 367-9
  • Peer Reviewed
• [Journal Article] In vivo distribution and localization of chorein. (2007)
  • Author(s): Y.Kurano, M.Nakamura, M.Ichiba, M.Matsuda, E.Mizuno, M.Kato, A.Agemura, S.Izumo, A.Sano
  • Journal Title: Biochem.Biophys.Res.Comm. 353・2 Pages: 431-435
• [Journal Article] Brain-specific transcript variants of 5′and 3′ends of mouse VPS13A and VPS13C. (2007)
  • Author(s): E.Mizuno, M.Nakamura, A.Agemura, A.Kusumoto, M.Ichiba, Y.Kurano, S.Muroya, A.Sano
  • Journal Title: Biochem.Biophys.Res.Comm. 353・4 Pages: 902-907
• [Journal Article] Neurologic phenotypes associated with acanthocytosis. (2007)
  • Author(s): R.H.Walker, H.H.Jung, C.Dobson-Stone, L.Rampoldi, A.Sano, F.Tison, A.Danek
  • Journal Title: Neurology 68・2 Pages: 92-98
• [Journal Article] Gene expression and association analysis of vascular endothelial growth factor in major depressive disorder. (2007)
  • Author(s): J.Iga, S.Ueno, K.Yamauchi, S.Numata, S.Tayoshi-Shibuya, S.Kinouchi, M.Nakataki, Hongwei Song, Kazuhiko Hokoishi, Hirotaka Tanabe, A.Sano, T.Ohmori
  • Journal Title: Prog.Neuro Psychopharmacol. ＆ Biol.Psychiatry. 31・3 Pages: 658-663
• [Journal Article] Association of AKT1 Haplotypes with the Risk of Schizophrenia in Iranian Population. (2006)
  • Author(s): S.N.Bajestan, A.H.Sabouri, M.Nakamura, H.Takashima, M.R.Keikhaee, F.Behdani, Mohammad, R.F., M.R.Sargolzaee, M.N.Bajestan, Z.Sabouri, Es.Khayami, S.Haghighi, S.B.Hashemi, N.Eiraku, H.Tufani, H.Najmabadi, K.Arimura, A.Sano, M.Osame
  • Journal Title: Am.J.Med.Genet. 141B・4 Pages: 383-386
• [Journal Article] Gene expression and association analysis of LIM (PDLIM5) in major depression. (2006)
  • Author(s): J.Iga, S.Ueno, K.Yamauchi, S.Numata, I.Motoki, S.Tayoshi, S.Kinouchi, K.Ohta, H.Song, K.Morita, K.Rokutan, Hi.Tanabe, A.Sano, T.Ohmori
  • Journal Title: Neurosci.Lett. 400・3 Pages: 203-207
• [Journal Article] Chorein deficiency leads to upregulation of gephyrin and GABA A receptor. (2006)
  • Author(s): Y.Kurano, M.Nakamura, M.Ichiba, M.Matsuda, E.Mizuno, M.Kato, S.Izumo, A.Sano
  • Journal Title: Biochem.Biophys.Res.Comm. 351・2 Pages: 438-442
• [Journal Article] Self-mutilation in chorea-acanthocytosis - manifestation of movement disorder or psychopathology? (2006)
  • Author(s): R.H.Walker, Q.Liu, M.Ichiba, S.Muroya, M.Nakamura, A.Sano, G.Sclar
  • Journal Title: Mov.Disord. 21・12 Pages: 2268-2269
• [Book] Neuroacanthocytosis Syndromes I (2008)
  • Author(s): Sano A. I (R.H. Walker, S. Saiki and A. Danek eds.)
  • Publisher: Psychiatric Morbidity in Neuroacanthocytosis.