トップページ研究室紹介（分子総合医学）先端応用医学（基礎系） 神経遺伝情報学

先端応用医学（基礎系）

神経遺伝情報学

SD-Score: Prediction of aberrant splicing at the 5' splice site

i-Score Designer: siRNA designing tool

分子状水素医学シンポジウム

神経遺伝情報　独自ページへ

分野の紹介

　当分野は、生体防御学分野を改組し、2004年9月に神経疾患の病態・治療基礎研究を行うセクションとして新たに発足した。当研究室は、以下のA-Dの４つの研究テーマに取り組んでいる。

 

研究テーマA　先天性筋無力症候群の分子病態とその制御研究

A-1. 先天性筋無力症候群の病態研究


　先天性筋無力症候群(congenital myasthenic syndromes, CMS)は、神経筋接合部情報伝達の障害により病的な筋力低下と易疲労性が生じる疾患群である（図１）。CMSにおいて欠損が同定された分子を図１に赤字で示す。これらのうち我々は、(1) 神経終末に取り込まれたコリンからアセチルコリンを再合成するcholine acetyltransferase (ChAT)、(2) acetylcholinesteraseをシナプス基底膜にanchoringをするcollagen Q、(3) リガンド結合性イオンチャンネルのアセチルコリンレセプター(AChR)、(4) AChRを終板にclusteringさせるrapsyn、(5) AChRによる終板電位を感知し、筋活動電位を起こす骨格筋電位依存性ナトリウムチャンネルNaV1.4の遺伝子変異を同定しその機能解析を行ってきた。さらに我が国では１例のみしかCMSの確定診断をされていなかったが、我々が遺伝子診断を行うことにより11例のCMS症例を同定し、変異分子の機能解析を行っている。ABI社次世代シークエンサーSOLiDを用いた新規遺伝子変異の解析も行っている（図２・図３）。

図１ 先天性筋無力症候群で変異が報告されている神経筋接合部分子
図２ Exome Captureによる次世代シークエンサーSOLiD解析
図３ SOLiD解析により同定をした遺伝子変異の一例

A-2. Collagen Q欠損に対するタンパク標的療法の開発研究

　Collagen Q遺伝子変異による先天性筋無力症候群(CMS)に対する治療法は存在しない。Collagen Qを持つacetylcholinesterase (非対称性AChE)（図４）は、形質導入COS細胞から細胞外に放出される。また、非対称性AChEはシナプス基底膜に係留をするシグナルを有している。従って、リンパ球もしくはiPS細胞、さらに骨格筋に正常collagen Qを導入することにより血中に発現をさせた非対称性AChEが、シナプス基底膜へ移行・係留をすると期待をされる（図５）。この治療法のfeasibilityをノックアウトマウスを用いて検証を行っている。また、このタンパク標的療法の、他の細胞外マトリックスタンパク欠損症・異常症への応用も行っている（図６）。

 

図４ 骨格筋に発現する６種類のactetylcholinesterase分子
図５ COLQ遺伝子欠損モデル動物に対するタンパク標的治療法
図６ タンパク標的治療法の候補分子と疾患

研究テーマB　正常ならびに各種神経筋疾患におけるRNA病態と制御研究

B-1. スプライシング病態研究


　ヒトは22,000個という限られた数の遺伝子から多様なタンパク質を作るために、組織特異的・発達段階特異的なalternative splicingを行っている。Alternative splicingは各遺伝子上のsplicing cis-elementsと、組織特異的・発達段階特異的に発現するsplicing trans-factorsによりコントロールされている（図７）。Splicing cis-elementsはエクソン上にも存在しexonic splicing enhancers (ESEs)/silencers (ESSs)と呼ばれる。また、弱いスプライシングシグナルを有するエクソンでは、constitutive splicingを受けるエクソンでも、splicing cis-elementsが重要な役割を担っている。当研究室では、splicing cis-elementsを破壊する遺伝子変異を同定し、さらにそのcis-elementsに結合をする分子を決定し、さらに、aberrant splicingを矯正する薬剤のスクリーニングを行っている（図８）。

 

図７ Splicing cis-elementsとtrans-factors
図８ CHRNA1遺伝子IVS3-8G>A変異はhnRNP Hの結合を減弱する。タンニン酸はPTBの発現を誘導することによりIVS3-8G>Aによるスプライシング異常を補正する。

B-2. ヒト正常splicing cis-elementsの研究


　クラシカルなsplicing cis-elementsには、branch point sequence, polypyrimidine tract, 3’ splice site, 5’ splice siteが知られている。これらのcis-elementsはdegenerativeなため、これらを破壊する遺伝子変異のsplicingに与える影響の予測は困難であった。我々は5’ splice siteのsplicing signalの強さを評価するSD Scoreを開発しウェブサービスプログラムを提供している（図９）。また、ヒトのbranch point consensus配列は、酵母のbranch point配列との類似性から導き出されているに過ぎず、branch point配列を破断する遺伝子変異のsplicingに与える効果は予測困難であった。我々は実験によりヒトbranch point consensus配列がyUnAyであることを明らかにした（図１０）。さらに、エクソンの第１塩基の塩基置換によりスプライシング異常を起こす疾患関連遺伝子変異が知られており、我々はその分子機構の解明を行っている（図１１）。

 

図９ SD-Scoreアルゴリズムは5’ splice siteの遺伝子変異のsplicingに対する効果を97.1%のsensitivityと94.7%のspecificityで予測する
図１０ ヒトbranch pointコンセンサス配列のpictogram (A)とWebLogo (B)
図１１ エクソン第１塩基の変異によりエクソンスキッピングを起こす遺伝子(FECH, GH1)と起こさない遺伝子(LPL, HEXA)

B-3. siRNA設計アルゴリズムの開発研究


　RNA interferenceは、安易かつ確実な遺伝子発現抑制機構として、近年盛んに用いられてきている。siRNAは、標的配列により効果が大きく異なり、優れたsiRNA設計アルゴリズムが必須である。我々は、効率的に遺伝子発現抑制予測が可能なアルゴリズムiScoreを開発し（図１２・図１３）、同時に別の8種類の既報告siRNA設計ツールの解析結果を計算をするウェブサービスを行っている。我々は、iScore Designerを用いることにより、2つのsiRNAに1つの割合で20%以下まで発現抑制が可能な効率のよいsiRNAの設計を日常的に行っている。
図１２ 効率的なsiRNA設計アルゴリズムiScoreは他の３種類の第２世代の設計アルゴリズムと同等の感度と特異度を示す
図１３　 iScoreを用いて熱不安定性の高いsiRNAを選ぶことにより従来のアルゴリズムを超える感度と特異度を得ることができる

研究テーマC　オフラベル薬効の研究　

C-1. 各種神経・筋・骨格疾患に対するオフラベル薬効の研究


　消炎鎮痛剤アスピリンの抗血小板作用・βブロッカープロプラノロールの本態性振戦抑制作用・睡眠薬サリドマイドの抗腫瘍作用・抗ウィルス薬アマンタジンや抗てんかん薬ゾニサミドの抗パーキンソン病作用など既認可薬のオフラベル薬効の臨床応用が行なわれてきている。難治性オーファン疾患はマーケット規模が小さいために製薬企業は新薬の開発をゼロから手がけるような多額の投資を行なうことができない。一方、既認可薬は用量・用法・安全域・副作用が知られており、培養細胞・モデル動物を使った研究成果の安価で迅速な臨床応用が可能であると期待をされる。我々は研究テーマB-1でも紹介をしたように先天性筋無力症候群、筋強直性ジストロフィー、進行性骨化性線維異形成症など各種筋疾患・骨疾患に対して既認可薬を用いたスクリーニングを行いいくつかの有効な薬剤を同定してきており、一部臨床研究を開始している。

 

研究テーマD　分子状水素の研究

D-1. 分子状水素の各種疾患に対する効果の検証とその分子作用機構の研究


　2007年6月に2%吸入水素の脳梗塞に対する効果が報告されて以来、飲用水または吸入気体としての分子状水素が、肝虚血・心筋梗塞・新生児脳虚血・腸管移植・シスプラチン腎毒性・認知症・糖尿病・動脈硬化症・難聴・舌癌・寄生虫肝炎・潰瘍性大腸炎・ウィルス性肝炎・網膜虚血・腎移植・I型アレルギーの合計17種類の病態に対して顕著な効果があることが報告されてきた。これらは酸化ストレス関連病態13種類と酸化ストレス非関連炎症病態4種類に分類をされる。
　我々は分子状の6-hydroxydopamine (6-OHDA)誘発パーキンソン病モデルラットに対する発症抑制効果の検証を行い顕著な発症抑制効果と疾病の進行抑制効果を認めた（図１４・図１５）。6-OHDA投与1週間前から～50％飽和水素水を自由飲水させた。水素水投与群全例においてパーキンソン病の発症をほぼ完全に抑制した。また、黒質ドパミン神経細胞数はコントロール群では健側の40%まで低下したのに対して、水素水投与群では83%まで維持されていた（図１６）。6-OHDA投与3日後からの水素水投与でもパーキンソン病進展予防効果を認め、水素水の投与はパーキンソン病モデルラットに極めて有効であることが示された。現在、各種病態ヒト・モデル動物・培養細胞における至適水素投与プロトコールの確立とその作用分子機構の解明に取り組んでいる。
　
図１４　コントロール水を飲用した片側性パーキンソン病モデルラットはamphetamine負荷により回転する[movie]。
図１５ 水素水を飲用した片側性パーキンソン病モデルラットはamphetamine負荷によっても回転しない。[movie]
図１６ 水素水飲用はドパミン神経細胞死を効率よく抑制する。6-OHDA投与3日後からの水素水投与も同様にドパミン神経細胞死を抑制する。

連絡先

○ 電話番号       052-744-2447

 

○ FAX               052-744-2449

 

○ 所在地           〒466-8550

　　　　　              名古屋市昭和区鶴舞町65

　　　　　              名古屋大学大学院医学系研究科神経遺伝情報学

　　　　　              （研究棟2号館　４階）

 

　2号館

教員

構成員名/英名表記 役職 所属
大野　欽司／OHNO　Kinji
詳しくはこちら→		教授神経遺伝情報学
増田　章男／MASUDA Akio
詳しくはこちら→		助教神経遺伝情報学
伊藤　美佳子／ITO Mikako
詳しくはこちら→		助教神経遺伝情報学
大河原　美静／OHKAWARA Bisei
詳しくはこちら→		特任助教神経遺伝情報学
大江　賢治／OHE Kenji
GCOE特任助教神経遺伝情報学

研究分野紹介

専攻 分子総合医学専攻
分野 神経遺伝情報学

大学院生入学案内

大学院生募集

当研究室は、「神経筋接合部」「RNA代謝」「オフラベル薬効」「分子状水素」をキーワードに、DNA、RNA、タンパク、細胞、モデル動物の各レベルのin vtiro, in vivo研究に加えて、コンピュータプログラム開発を伴うin silico研究を行っています。これらの研究分野に興味のある修士課程（２年間）・博士課程（４年間）の大学院生を募集しています。また、３年次学士入学者も受け入れております。

将来を嘱望される研究者を育てることが私たちの重要な責務であると思っております。

 

入試

修士課程は8月下旬に医学生物学・英語の筆記試験と面接があります。日本語の筆記試験ですが、留学生用に自己推薦入試システムもあります。博士課程は1月下旬（国内学生・留学生）と9月下旬（留学生）に英語と専門科目の筆記試験があります。博士課程は英語で筆記試験を受けることができます。両過程ともご相談下さい。

研究業績

Original Articles (Published in English)

  1. Ito M, Suzuki Y, Okada T, Fukudome T, Yoshimura T, Masuda A, Takeda S, Krejci E, Ohno K. Protein-anchoring strategy for delivering acetylcholinesterase to the neuromuscular junction. Mol Ther in press. PubMed
  2. Matsuura T, Minami N, Arahata H, Ohno K, Abe K, Hayashi YK, Nishino I. Myotonic dystrophy type 2 (DM2) is rare in the Japanese population. J Hum Genet in press.
  3. Yoshinaga H, Sakoda S, Good JM, Takahashi MP, Kubota T, Arikawa-Hirasawa E, Nakata T, Ohno K, Kitamura T, Kobayashi K, Ohtsuka Y. A novel mutation in SCN4A causes severe myotonia and school-age-onset paralytic episodes. J Neurol Sci in press. PubMed
  4. Masuda A, Andersen HS, Doktor TK, Okamoto T, Ito M, Andresen BS, Ohno K. CUGBP1 and MBNL1 preferentially bind to 3’ UTRs and facilitate mRNA decay. Scientific Reports 2012, 2: 209. PubMed
  5. Kawakami Y, Ito M, Hirayama M, Sahashi K, Ohkawara B, Masuda A, Nishida H, Mabuchi N, Engel A G, Ohno K. Anti-MuSK autoantibodies block binding of collagen Q to MuSK. NeurologyNeurology 2011, 77:1819-1826. PubMed
  6. Kaneko H, Kitoh H, Matsuura T, Masuda A, Ito M, Mottes M, Rauch F, Ishiguro N, Ohno K. Hyperuricemia cosegregating with osteogenesis imperfecta is associated with a mutation in GPATCH8. Hum Genet 130:671-683. PubMed
  7. Ito M, Ibi T, Sahashi K, Ichihara M, Ito M, Ohno K. Open-label trial and randomized, double-blind, placebo-controlled, crossover trial of hydrogen-enriched water for mitochondrial and inflammatory myopathies. Medical Gas Research 2011, 1:24.
  8. Selcen D, Juel V C, Hobson-Webb L D, Smith E C, Stickler D E, Bite A V, Ohno K, Engel A G. Myasthenic syndrome caused by plectinopathy. Neurology 2011, 76:327-336. PubMed
  9. Itoh T, Hamada N, Terazawa R, Ito M, Ohno K, Ichihara M, Nozawa Y. Molecular hydrogen inhibits lipopolysaccharide/interferon gamma-induced nitric oxide production through modulation of signal transduction in macrophages. Biochem Biophys Res Commun 2011, 411:143-149. PubMed
  10. Hirayama M, Nakamura T, Watanabe H, Uchida K, Hama T, Hara T, Niimi Y, Ito M, Ohno K, Sobue G. Urinary 8-hydroxydeoxyguanosine correlate with hallucinations rather than motor symptoms in Parkinson's disease. Parkinsonism Relat Disord 2011, 17:46-49. PubMed
  11. Fu Y, Masuda A, Ito M, Shinmi J, Ohno K. AG-dependent 3'-splice sites are predisposed to aberrant splicing due to a mutation at the first nucleotide of an exon. Nucleic Acids Research 2011, 39:4396-4404. PubMed
  12. Milone M, Shen X-M, Selcen D, Ohno K, Brengman J, Iannaccone S T, Harper C M, Engel A G. Myasthenic syndrome due to defects in rapsyn: Clinical and molecular findings in 39 patiens. Neurology 2009, 73:228-235. PubMed
  13. Kurosaki T, Matsuura T, Ohno K, Ueda S. Alu-mediated acquisition of unstable ATTCT pentanucleotide repeats in the human ATXN10 gene. Mol Biol Evol 2009, 26:2573-2579. PubMed
  14. Itoh T, Fujita Y, Ito M, Masuda A, Ohno K, Ichihara M, Kojima T, Nozawa Y, Ito M. Molecular hydrogen suppresses Fc epsilon RI-mediated signal transduction and prevents degranulation of mast cells. Biochem Bioph Res Co 2009, 389:651-656. PubMed
  15. Fu Y, Ito M, Fujita Y, Ito M, Ichihara M, Masuda A, Suzuki Y, Maesawa S, Kajita Y, Hirayama M, Ohsawa I, Ohta S, Ohno K. Molecular hydrogen is protective against 6-hydroxydopamine-induced nigrostriatal degeneration in a rat model of Parkinson’s disease. Neuroscience Letters 2009, 453:81?85. PubMed
  16. Bian Y, Masuda A, Matsuura T, Ito M, Okushin K, Engel A G, Ohno K. Tannic acid facilitates expression of the polypyrimidine tract binding protein and alleviates deleterious inclusion of CHRNA1 exon P3A due to an hnRNP H-disrupting mutation in congenital myasthenic syndrome. Hum Mol Genet 2009, 18:1229-1237. PubMed
  17. Almeida T, Alonso I, Martins S, Ramos E M, Azevedo L, Ohno K, Amorim A, Saraiva-Pereira M L, Jardim L B, Matsuura T, Sequeiros J, Silveira I. Ancestral origin of the ATTCT repeat expansion in spinocerebellar ataxia type 10 (SCA10). PLoS ONE 2009, 4:e4553. PubMed
  18. Shen X M, Fukuda T, Ohno K, Sine S M, Engel A G. Congenital myasthenia-related AChR delta subunit mutation interferes with intersubunit communication essential for channel gating. J Clin Invest 2008, 118:1867-1876. PubMed
  19. Saito T, Amakusa Y, Kimura T, Yahara O, Aizawa H, Ikeda Y, Day J W, Ranum L P, Ohno K, Matsuura T. Myotonic dystrophy type 2 in Japan: ancestral origin distinct from Caucasian families. Neurogenetics 2008, 9:61-63. PubMed
  20. Masuda A, Shen X M, Ito M, Matsuura T, Engel A G, Ohno K. hnRNP H enhances skipping of a nonfunctional exon P3A in CHRNA1 and a mutation disrupting its binding causes congenital myasthenic syndrome. Hum Mol Genet 2008, 17:4022-4035. PubMed
  21. Kurosaki T, Matsuura T, Ohno K, Ueda S. Long-range PCR for the diagnosis of spinocerebellar ataxia type 10. Neurogenetics 2008, 9:151-152. PubMed
  22. Ito M, Masuda A, Jinno S, Katagiri T, Krejci E, Ohno K. Viral vector-medicated expression of human collagen Q in cultured cells. Chem Biol Interact 2008, 175:346-348. PubMed
  23. Gao K, Masuda A, Matsuura T, Ohno K. Human branch point consensus sequence is yUnAy. Nucleic Acids Res 2008, 36:2257-2267. PubMed
  24. Sahashi K, Masuda A, Matsuura T, Shinmi J, Zhang Z, Takeshima Y, Matsuo M, Sobue G, Ohno K. In vitro and in silico analysis reveals an efficient algorithm to predict the splicing consequences of mutations at the 5' splice sites. Nucleic Acids Res 2007, 35:5995-6003. PubMed
  25. Masuda A, Hashimoto K, Yokoi T, Doi T, Kodama T, Kume H, Ohno K, Matsuguchi T. Essential role of GATA transcriptional factors in the activation of mast cells. J Immunol 2007, 178:360-368. PubMed
  26. Ichihara M, Murakumo Y, Masuda A, Matsuura T, Asai N, Jijiwa M, Ishida M, Shinmi J, Yatsuya H, Qiao S, Takahashi M, Ohno K. Thermodynamic instability of siRNA duplex is a prerequisite for dependable prediction of siRNA activities. Nucleic Acids Res 2007, 35:e123. PubMed
  27. Shen X-M, Ohno K, Sine S M, Engel A G. Subunit-specific contribution to agonist binding and channel gating revealed by inherited mutation in muscle acetylcholine receptor M3-M4 linker. Brain 2005, 128:345-355. PubMed
  28. , Tsujino A, Shen X-M, Milone M, Engel A G. Spectrum of splicing errors caused by CHRNE mutations affecting introns and intron/exon boundaries. J Med Genet 2005, 42:e53. PubMed
  29. Selcen D, Ohno K, Engel A G. Myofibrillar myopathy: clinical, morphological and genetic studies in 63 patients. Brain 2004, 127:439-451. PubMed
  30. Sahashi K, Ibi T, Ohno K, Sahashi K, Nakao N, Kondo H. Progressive myopathy with circulating autoantibody against giantin in the Golgi apparatus. Neurology 2004, 62:1891-1893. PubMed
  31. Ohno K, Engel A G. Lack of founder haplotype for the rapsyn N88K mutation: N88K is an ancient founder mutation or arises from multiple founders. J Med Genet 2004, 41:e8. PubMed
  32. Kimbell L M, Ohno K, Engel A G, Rotundo R L. C-terminal and heparin-binding domains of collagenic tail subunit are both essential for anchoring acetylcholinesterase at the synapse. J Biol Chem 2004, 279:10997-11005. PubMed
  33. Cai Y, Cronin C N, Engel A G, Ohno K, Hersh L B, Rodgers D W. Choline acetyltransferase structure reveals distribution of mutations that cause motor disorders. Embo J 2004, 23:2047-2058. PubMed
  34. Banwell B L, Ohno K, Sieb J P, Engel A G. Novel truncating RAPSN mutations causing congenital myasthenic syndrome responsive to 3,4-diaminopyridine. Neuromuscul Disord 2004, 14:202-207. PubMed
  35. Tsujino A, Maertens C, Ohno K, Shen X-M, Fukuda T, Harper C M, Cannon S C, Engel A G. Myasthenic syndrome caused by mutation of the SCN4A sodium channel. Proc Natl Acad Sci U S A 2003, 100:7377-7382. PubMed
  36. Shen X-M, Ohno K, Tsujino A, Brengman J M, Gingold M, Sine S M, Engel A G. Mutation causing severe myasthenia reveals functional asymmetry of AChR signature cystine loops in agonist binding and gating. J Clin Invest 2003, 111:497-505. PubMed
  37. Ohno K, Sadeh M, Blatt I, Brengman J M, Engel A G. E-box mutations in the RAPSN promoter region in eight cases with congenital myasthenic syndrome. Hum Mol Genet 2003, 12:739-748. PubMed
  38. Ohno K, Milone M, Shen X-M, Engel A G. A frameshifting mutation in CHRNE unmasks skipping of the preceding exon. Hum Mol Genet 2003, 12:3055-3066. PubMed
  39. Sine S M, Shen X-M, Wang H-L, Ohno K, Lee W-Y, Tsujino A, Brengmann J, Bren N, Vajsar J, Engel A G. Naturally occurring mutations at the acetylcholine receptor binding site independently alter ACh binding and channel gating. J Gen Physiol 2002, 120:483-496. PubMed
  40. Shen X-M, Ohno K, Fukudome T, Tsujino A, Brengman J M, De Vivo D C, Packer R J, Engel A G. Congenital myasthenic syndrome caused by low-expressor fast-channel AChR delta subunit mutation. Neurology 2002, 59:1881-1888. PubMed
  41. Shapira Y A, Sadeh M E, Bergtraum M P, Tsujino A, Ohno K, Shen X-M, Brengman J, Edwardson S, Matoth I, Engel A G. Three novel COLQ mutations and variation of phenotypic expressivity due to G240X. Neurology 2002, 58:603-609. PubMed
  42. Ohno K, Engel A G, Shen X-M, Selcen D, Brengman J, Harper C M, Tsujino A, Milone M. Rapsyn mutations in humans cause endplate acetylcholine-receptor deficiency and myasthenic syndrome. Am J Hum Genet 2002, 70:875-885. PubMed
  43. Byring R F, Pihko H, Tsujino A, Shen X-M, Gustafsson B, Hackman P, Ohno K, Engel A G, Udd B. Congenital myasthenic syndrome associated with episodic apnea and sudden infant death. Neuromuscul Disord 2002, 12:548-553. PubMed mso-fareast-theme-font: minor-latin; mso-bidi-font-family: Century; mso-bidi-theme-font: minor-latin" lang=EN-US>40.Sahashi K, Yoneda M, Ohno K, Tanaka M, Ibi T. Functional characterisation of mitochondrial tRNA(Tyr) mutation (5877-->GA) associated with familial chronic progressive external ophthalmoplegia. J Med Genet 2001, 38:703-705. PubMed
  44. Ohno K, Tsujino A, Brengman J M, Harper C M, Bajzer Z, Udd B, Beyring R, Robb S, Kirkham F J, Engel A G. Choline acetyltransferase mutations cause myasthenic syndrome associated with episodic apnea in humans. Proc Natl Acad Sci U S A 2001, 98:2017-2022. PubMed
  45. Wang H-L, Ohno K, Milone M, Brengman J M, Evoli A, Batocchi A P, Middleton L T, Christodoulou K, Engel A G, Sine S M. Fundamental gating mechanism of nicotinic receptor channel revealed by mutation causing a congenital myasthenic syndrome. J Gen Physiol 2000, 116:449-462. PubMed
  46. Ohno K, Engel A G, Brengman J M, Shen X-M, Heidenreich F, Vincent A, Milone M, Tan E, Demirci M, Walsh P, Nakano S, Akiguchi I. The spectrum of mutations causing end-plate acetylcholinesterase deficiency. Ann Neurol 2000, 47:162-170. PubMed
  47. Wang H-L, Milone M, Ohno K, Shen X-M, Tsujino A, Batocchi A P, Tonali P, Brengman J, Engel A G, Sine S M. Acetylcholine receptor M3 domain: stereochemical and volume contributions to channel gating. Nat Neurosci 1999, 2:226-233. PubMed
  48. Quiram P A, Ohno K, Milone M, Patterson M C, Pruitt N J, Brengman J M, Sine S M, Engel A G. Mutation causing congenital myasthenia reveals acetylcholine receptor beta/delta subunit interaction essential for assembly. J Clin Invest 1999, 104:1403-1410. PubMed
  49. Ohno K, Brengman J M, Felice K J, Cornblath D R, Engel A G. Congenital end-plate acetylcholinesterase deficiency caused by a nonsense mutation and an A-->G splice-donor-site mutation at position +3 of the collagenlike-tail-subunit gene (COLQ): how does G at position +3 result in aberrant splicing? Am J Hum Genet 1999, 65:635-644. PubMed
  50. Ohno K, Anlar B, Engel A G. Congenital myasthenic syndrome caused by a mutation in the Ets-binding site of the promoter region of the acetylcholine receptor epsilon subunit gene. Neuromuscul Disord 1999, 9:131-135. PubMed
  51. Middleton L, Ohno K, Christodoulou K, Brengman J, Milone M, Neocleous V, Serdaroglu P, Deymeer F, Ozdemir C, Mubaidin A, Horany K, Al-Shehab A, Mavromatis I, Mylonas I, Tsingis M, Zamba E, Pantzaris M, Kyriallis K, Engel A G. Chromosome 17p-linked myasthenias stem from defects in the acetylcholine receptor epsilon-subunit gene. Neurology 1999, 53:1076-1082. PubMed
  52. Ohno K, Brengman J, Tsujino A, Engel A G. Human endplate acetylcholinesterase deficiency caused by mutations in the collagen-like tail subunit (ColQ) of the asymmetric enzyme. Proc Natl Acad Sci U S A 1998, 95:9654-9659. PubMed
  53. Ohno K, Anlar B, Ozdirim E, Brengman J M, Engel A G. Frameshifting and splice-site mutations in the acetylcholine receptor epsilon subunit gene in three Turkish kinships with congenital myasthenic syndromes. Ann N Y Acad Sci 1998, 841:189-194. PubMed
  54. Ohno K, Anlar B, Ozdirim E, Brengman J M, DeBleecker J L, Engel A G. Myasthenic syndromes in Turkish kinships due to mutations in the acetylcholine receptor. Ann Neurol 1998, 44:234-241. PubMed
  55. Milone M, Wang H-L, Ohno K, Prince R, Fukudome T, Shen X-M, Brengman J M, Griggs R C, Sine S M, Engel A G. Mode switching kinetics produced by a naturally occurring mutation in the cytoplasmic loop of the human acetylcholine receptor epsilon subunit. Neuron 1998, 20:575-588. PubMed
  56. Milone M, Ohno K, Fukudome T, Shen X-M, Brengman J, Griggs R C, Engel A G. Congenital myasthenic syndrome caused by novel loss-of-function mutations in the human AChR epsilon subunit gene. Ann N Y Acad Sci 1998, 841:184-188. PubMed
  57. Fukudome T, Ohno K, Brengman J M, Engel A G. Quinidine normalizes the open duration of slow-channel mutants of the acetylcholine receptor. Neuroreport 1998, 9:1907-1911. PubMed
  58. Fukudome T, Ohno K, Brengman J M, Engel A G. AChR channel blockade by quinidine sulfate reduces channel open duration in the slow-channel congenital myasthenic syndrome. Ann N Y Acad Sci 1998, 841:199-202. PubMed
  59. Wang H-L, Auerbach A, Bren N, Ohno K, Engel A G, Sine S M. Mutation in the M1 domain of the acetylcholine receptor alpha subunit decreases the rate of agonist dissociation. J Gen Physiol 1997, 109:757-766. PubMed
  60. Ohno K, Quiram P A, Milone M, Wang H-L, Harper M C, Pruitt J N, 2nd, Brengman J M, Pao L, Fischbeck K H, Crawford T O, Sine S M, Engel A G. Congenital myasthenic syndromes due to heteroallelic nonsense/missense mutations in the acetylcholine receptor epsilon subunit gene: identification and functional characterization of six new mutations. Hum Mol Genet 1997, 6:753-766. PubMed
  61. Milone M, Wang H-L, Ohno K, Fukudome T, Pruitt J N, Bren N, Sine S M, Engel A G. Slow-channel myasthenic syndrome caused by enhanced activation, desensitization, and agonist binding affinity attributable to mutation in the M2 domain of the acetylcholine receptor alpha subunit. J Neurosci 1997, 17:5651-5665. PubMed
  62. Sawano T, Tanaka M, Ohno K, Yoneda M, Ota Y, Terasaki H, Awaya S, Ozawa T. Mitochondrial DNA mutations associated with the 11778 mutation in Leber's disease. Biochem Mol Biol Int 1996, 38:693-700. PubMed
  63. Ohno K, Yamamoto M, Engel A G, Harper C M, Roberts L R, Tan G H, Fatourechi V. MELAS- and Kearns-Sayre-type co-mutation [corrected] with myopathy and autoimmune polyendocrinopathy. Ann Neurol 1996, 39:761-766. PubMed
  64. Ohno K, Wang H-L, Milone M, Bren N, Brengman J M, Nakano S, Quiram P, Pruitt J N, Sine S M, Engel A G. Congenital myasthenic syndrome caused by decreased agonist binding affinity due to a mutation in the acetylcholine receptor epsilon subunit. Neuron 1996, 17:157-170. PubMed
  65. Engel A G, Ohno K, Milone M, Wang H-L, Nakano S, Bouzat C, Pruitt J N, 2nd, Hutchinson D O, Brengman J M, Bren N, Sieb J P, Sine S M. New mutations in acetylcholine receptor subunit genes reveal heterogeneity in the slow-channel congenital myasthenic syndrome. Hum Mol Genet 1996, 5:1217-1227. PubMed
  66. Engel A G, Ohno K, Bouzat C, Sine S M, Griggs R C. End-plate acetylcholine receptor deficiency due to nonsense mutations in the epsilon subunit. Ann Neurol 1996, 40:810-817. PubMed
  67. Sine S M, Ohno K, Bouzat C, Auerbach A, Milone M, Pruitt J N, Engel A G. Mutation of the acetylcholine receptor alpha subunit causes a slow-channel myasthenic syndrome by enhancing agonist binding affinity. Neuron 1995, 15:229-239. PubMed
  68. Ohno K, Hutchinson D O, Milone M, Brengman J M, Bouzat C, Sine S M, Engel A G. Congenital myasthenic syndrome caused by prolonged acetylcholine receptor channel openings due to a mutation in the M2 domain of the epsilon subunit. Proc Natl Acad Sci U S A 1995, 92:758-762. PubMed
  69. Suoh H, Sahashi K, Ibi T, Tashiro M, Tanaka F, Mitsuma T, Ohno K. Progressive external ophthalmoplegia and myositis. Internal Med 1993, 32:319-322. PubMed
  70. Sano T, Ban K, Ichiki T, Kobayashi M, Tanaka M, Ohno K, Ozawa T. Molecular and genetic analyses of two patients with Pearson's marrow-pancreas syndrome. Pediatr Res 1993, 34:105-110. PubMed
  71. Sahashi K, Tanaka M, Tashiro M, Ohno K, Ibi T, Takahashi A, Ozawa T. Increased mitochondrial DNA deletions in the skeletal muscle of myotonic dystrophy. Gerontology 1992, 38:18-29. PubMed
  72. Tanaka M, Ino H, Ohno K, Ohbayashi T, Ikebe S, Sano T, Ichiki T, Kobayashi M, Wada Y, Ozawa T. Mitochondrial DNA mutations in mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes (MELAS). Biochem Biophys Res Commun 1991, 174:861-868. PubMed
  73. Ozawa T, Tanaka M, Sugiyama S, Ino H, Ohno K, Hattori K, Ohbayashi T, Ito T, Deguchi H, Kawamura K. Patients with idiopathic cardiomyopathy belong to the same mitochondrial DNA gene family of Parkinson's disease and mitochondrial encephalomyopathy. Biochem Biophys Res Commun 1991, 177:518-525. PubMed
  74. Ozawa T, Tanaka M, Ino H, Ohno K, Sano T, Wada Y, Yoneda M, Tanno Y, Miyatake T, Tanaka T. Distinct clustering of point mutations in mitochondrial DNA among patients with mitochondrial encephalomyopathies and with Parkinson's disease. Biochem Biophys Res Commun 1991, 176:938-946. PubMed
  75. Ota Y, Tanaka M, Sato W, Ohno K, Yamamoto T, Maehara M, Negoro T, Watanabe K, Awaya S, Ozawa T. Detection of platelet mitochondrial DNA deletions in Kearns-Sayre syndrome. Invest Ophthalmol Vis Sci 1991, 32:2667-2675. PubMed
  76. Ohno K, Tanaka M, Suzuki H, Ohbayashi T, Ikebe S, Ino H, Kumar S, Takahashi A, Ozawa T. Identification of a possible control element, Mt5, in the major noncoding region of mitochondrial DNA by intraspecific nucleotide conservation. Biochem Int 1991, 24:263-272. PubMed
  77. Ohno K, Tanaka M, Sahashi K, Ibi T, Sato W, Yamamoto T, Takahashi A, Ozawa T. Mitochondrial DNA deletions in inherited recurrent myoglobinuria. Ann Neurol 1991, 29:364-369. PubMed
  78. Ohno K, Tanaka M, Ino H, Suzuki H, Tashiro M, Ibi T, Sahashi K, Takahashi A, Ozawa T. Direct DNA sequencing from colony: analysis of multiple deletions of mitochondrial genome. Biochim Biophys Acta 1991, 1090:9-16. PubMed
  79. Ino H, Tanaka M, Ohno K, Hattori K, Ikebe S, Sano T, Ozawa T, Ichiki T, Kobayashi M, Wada Y. Mitochondrial leucine tRNA mutation in a mitochondrial encephalomyopathy. Lancet 1991, 337:234-235. PubMed
  80. Tanaka M, Ino H, Ohno K, Hattori K, Sato W, Ozawa T, Tanaka T, Itoyama S. Mitochondrial mutation in fatal infantile cardiomyopathy. Lancet 1990, 336:1452. PubMed
  81. Sahashi K, Ohno K, Tanaka M, Ibi T, Yamamoto T, Tashiro M, Sato W, Takahashi A, Ozawa T. Cytoplasmic body and mitochondrial DNA deletion. J Neurol Sci 1990, 99:291-300. PubMed
  82. Ozawa T, Tanaka M, Sugiyama S, Hattori K, Ito T, Ohno K, Takahashi A, Sato W, Takada G, Mayumi B. Multiple mitochondrial DNA deletions exist in cardiomyocytes of patients with hypertrophic or dilated cardiomyopathy. Biochem Biophys Res Commun 1990, 170:830-836. PubMed
  83. Ozawa T, Tanaka M, Ikebe S, Ohno K, Kondo T, Mizuno Y. Quantitative determination of deleted mitochondrial DNA relative to normal DNA in parkinsonian striatum by a kinetic PCR analysis. Biochem Biophys Res Commun 1990, 172:483-489. PubMed
  84. Ikebe S, Tanaka M, Ohno K, Sato W, Hattori K, Kondo T, Mizuno Y, Ozawa T. Increase of deleted mitochondrial DNA in the striatum in Parkinson's disease and senescence. Biochem Biophys Res Commun 1990, 170:1044-1048. PubMed
  85. Tanaka-Yamamoto T, Tanaka M, Ohno K, Sato W, Horai S, Ozawa T. Specific amplification of deleted mitochondrial DNA from a myopathic patient and analysis of deleted region with S1 nuclease. Biochim Biophys Acta 1989, 1009:151-155. PubMed
  86. Tanaka M, Yoneda M, Ohno K, Sato W, Yamamoto M, Nonaka I, Horai S, Ozawa T. Differently deleted mitochondrial genomes in maternally inherited chronic progressive external ophthalmoplegia. J Inherit Metab Dis 1989, 12:359-362. PubMed
  87. Tanaka M, Sato W, Ohno K, Yamamoto T, Ozawa T. Direct sequencing of deleted mitochondrial DNA in myopathic patients. Biochem Biophys Res Commun 1989, 164:156-163. PubMed
  88. Sato W, Tanaka M, Ohno K, Yamamoto T, Takada G, Ozawa T. Multiple populations of deleted mitochondrial DNA detected by a novel gene amplification method. Biochem Biophys Res Commun 1989, 162:664-672. PubMed
  89. Ozawa T, Yoneda M, Tanaka M, Ohno K, Sato W, Suzuki H, Nishikimi M, Yamamoto M, Nonaka I, Horai S. Maternal inheritance of deleted mitochondrial DNA in a family with mitochondrial myopathy. Biochem Biophys Res Commun 1988, 154:1240-1247. PubMed

Reviews and Chapters in Books (Published in English)

  1. Ohno K, Ito M, Engel A G. 2011. Congenital Myasthenic Syndromes - Molecular Bases of Congenital Defects of Proteins at the Neuromuscular Junction - In Myopathy. Rijeka: InTech. in press.
  2. Engel A G, Shen X-M, Ohno K, Sine S M. 2011. Congenital myasthenic syndromes. In Myasthenia gravis and myasthenic disorders 2nd ed. A.G. Engel, editor. New York: Oxford University Press. in press.
  3. Ohno K, Engel A G. 2011. Chapter 8: Molecular defects of acetylcholine receptor subunits in congenital myasthenic syndromes. In Pharmacology of Nicotinic Acetylcholine Receptors from the Basic and Therapeutic Perspectives. H.R. Arias, editor. Kerala: Research Signpost. pp175-186.
  4. Ohta S, Nakao A, Ohno K. The 2011 Medical Molecular Hydrogen Symposium: An Inaugural Symposium of the Journal Medical Gas Research. Medical Gas Research 2011, 1:10. PubMed
  5. Ohno K, Masuda A. 2011. RNA pathologies in neurological disorders. In Neurochemical Mechanisms in Disease, Advances in Neurobiology. A. Lajtha, editor. New York: Springer. 399-415.
  6. Ohno K, Engel A G. Splicing abnormalities in congenital myasthenic syndromes. Acta Myologica 2005, 24:50-54. PubMed
  7. Sine S M, Engel A G, Wang H-L, Ohno K. 2004. Molecular Insights into Acetylcholine Receptor Structure and Function Revealed by Mutations Causing Congenital Myasthenic Syndromes. In Molecular and Cellular Insights into Ion Channel Biology. R.A. Maue, editor. Amsterdam: Elsevier Science. 95-119.
  8. Engel A G, Ohno K, Sine S M. 2004. Congenital myasthenic syndromes (Chapter 66). In Myology. A.G. Engel, and C. Franzini-Armstrong, editors. New York: McGraw Hill. 1801-1844.
  9. Sine S M, Wang H L, Ohno K, Shen X M, Lee W Y, Engel A G. Mechanistic diversity underlying fast channel congenital myasthenic syndromes. Ann N Y Acad Sci 2003, 998:128-137. PubMed
  10. Engel A G, Ohno K, Sine S M. Congenital myasthenic syndromes: A diverse array of molecular targets. J Neurocytol 2003, 32:1017-1037. PubMed
  11. Engel A G, Ohno K, Sine S M. Neurological diseases: Sleuthing molecular targets for neurological diseases at the neuromuscular junction. Nat Rev Neurosci 2003, 4:339-352. PubMed
  12. Engel A G, Ohno K, Sine S M. Congenital myasthenic syndromes: Progress over the past decade. Muscle Nerve 2003, 27:4-25. PubMed
  13. Engel A G, Ohno K, Shen X-M, Sine S M. Congenital Myasthenic Syndromes: Multiple Molecular Targets At The Neuromuscular Junction. Ann N Y Acad Sci 2003, 998:138-160.
  14. Engel A G, Ohno K, Harper C M. 2003. Congenital myasthenic syndromes. In Neuromuscular Disorders of Infancy, Childhood, and Adolescence: A Clinician's Approach. H.R. Jones, C. De Vivo D, and B.T. Darras, editors. Boston: Butterworth and Heinemann. 555-574.
  15. Ohno K, Engel A G. Congenital myasthenic syndromes: genetic defects of the neuromuscular junction. Curr Neurol Neurosci Rep 2002, 2:78-88. PubMed
  16. Engel A G, Ohno K, Sine S M. The spectrum of congenital myasthenic syndromes. Mol Neurobiol 2002, 26:347-367. PubMed
  17. Engel A G, Ohno K, Selcen D. 2002. Congenital Myasthenic Syndromes. In Structural and Molecular Basis of Skeletal Muscle Diseases. G. Karpati, editor. Basel: International Society of Neuropathology/World Federation of Neurology. ISN Neuropath Press. 170-179.
  18. Engel A G, Ohno K. 2002. Congenital myasthenic syndromes (Chapter 13). In Advances in Neurology. R. Pourmand, and Y. Harati, editors. Philadelphia: Lippincott Williams & Wilkins. 203-215.
  19. Engel A G, Ohno K, Sine S M. 2001. Acetylcholine receptor channelopathies and other congenital myasthenic syndromes (Chapter 12). In Channelopathies of the nervous system. M.R. Rose, and R.C. Griggs, editors. Boston: Butterworth and Heinemann. 179-191.
  20. Engel A G, Ohno K, Stans A A. 2000. Congenital myasthenic syndromes. In Neuromuscular Diseases: From Basic Mechanisms To Clinical Management. F. Demeer, editor. Basel: Karger. 96-112.
  21. Engel A G, Ohno K, Shen X M, Milone M, Tsujino A. Congenital myasthenic syndromes in the molecular era. Acta Myologica 2000, 19:5-21.
  22. Engel A G, Ohno K, Sine S M. 1999. Congenital myasthenic syndromes (Chapter 11). In Myasthenia gravis and myasthenic disorders. A.G. Engel, editor. New York: Oxford University Press. 251-297.
  23. Engel A G, Ohno K, Sine S M. Congenital myasthenic syndromes - Recent advances. Arch Neurol 1999, 56:163-167. PubMed
  24. Engel A G, Ohno K, Wang H-L, Milone M, Sine S M. The molecular basis of congenital myasthenic syndromes: Mutations in the acetylcholine receptor. The Neuroscientist 1998, 4:185-194.
  25. Engel A G, Ohno K, Sine S M. Congenital Myasthenic Syndromes - Experiments of Nature. J Physiol Paris 1998, 92:113-117. PubMed
  26. Engel A G, Ohno K, Milone M, Sine S M. Congenital myasthenic syndromes: New insights from molecular genetic and patch-clamp studies. Ann NY Acad Sci 1998, 841:140-156. PubMed
  27. Engel A G, Ohno K, Milone M, Sine S M. Congenital myasthenic syndromes caused by mutations in acetylcholine receptor genes. Neurology 1997, 48:S28-S35.
  28. Tanaka M, Hattori K, Ito H, Ohbayashi T, Ohno K, Sato W, Sugiyama S, Ozawa T. 1991. Mitochondrial DNA mutations in idiopathic cardiomyopathy and in presbycardia. In Mitochondrial Encephalomyopathies. T. Sato, editor. New York: Raven Press. 225-236.
  29. Sahashi K, Ibi T, Ohno K, Tanaka M, Tashiro M, Tsuchiya I, Nakao M, Yuasa K, Mitsuma T, Takahashi A, Ozawa T. 1991. Visceral myopathy with external ophthalmoplegia and multiple mitochondrial DNA deletions. In New Trends in Autonomic Nervous System Research. M.e.a. Yoshikawa, editor. B. V.: Elsevier Science Publishers. 229-230.
  30. Ozawa T, Tanaka M, Sato W, Ohno K, Yoneda M, Yamamoto T. 1991. Types and mechanism of mitochondrial DNA mutations in mitochondrial myopathy and related diseases. In Molecular Basis of Neurological Disorders and their Treatment. J.W. Gorrod, O. Albano, E. Ferrari, and S. Papa, editors. London: Chapman and Hall. 173-190.
  31. Ozawa T, Tanaka M, Sato W, Ohno K, Yoneda M. 1991. Diseases caused by mitochondrial DNA mutations: types and mechanism. In Proceedings of the XIth International Congress of Neuropathology. Tokyo: Jpn. Soc. Neuropathol. 481-485.
  32. Ozawa T, Tanaka M, Hayakawa M, Sugiyama S, Sato W, Ohno K, Ikebe S, Yoneda M. 1991. Mitochondrial DNA mutations: types, mechanism and expression. In Progress in Neuropathology Vol. 7, Mitochondrial Encephalomyopathies. T. Sato, editor. New York: Raven Press. 141-151.
  33. Ozawa T, Tanaka M, Hayakawa M, Sugiyama S, Ino H, Sato W, Ohno K, Ikebe S, Yoneda M. 1991. Mitochondrial DNA disease: phylogeny and expression. In New Era of Bioenergetics. Y. Mukohata, editor. Tokyo: Academic Press. 247-272.
  34. Tanaka M, Sato W, Ohno K, Yamamoto T, Ozawa T. 1990. S1 nuclease analysis and direct sequencing of deleted mitochondrial DNA in myopathic patients: Role of directly repeated sequences in deletion. In Bioenergetics: Molecular Biology, Biochemistry, and Pathology. C.H. Kim, and T. Ozawa, editors. New York: Plenum. 441-449.
  35. Ozawa T, Tanaka M, Sato W, Ohno K, Sugiyama S, Yoneda M, Yamamoto T, Hattori K, Ikebe S, Tashiro M, Sahashi K. 1990. Mitochondrial DNA mutations as an etiology of human degenerative diseases. In Bioenergetics: Molecular Biology, Biochemistry, and Pathology. C.H. Kim, and T. Ozawa, editors. New York and London: Plenum. 413-427.

Reviews and Chapters in Books (Published in Japanese)

 

1.        大野欽司「スプライシングシス因子の破断変異によるスプライシング異常」医学のあゆみ 238(5) 485-490, 2011.

2.        大野欽司「分子状水素のサイエンス」アンチ・エイジング医学- 日本抗加齢医学会雑誌 7(3) 378-387, 2011.

3.        大野欽司「神経筋接合部における遺伝子異常と疾患」脳と神経63(7): 669-678, 2011. PubMed

4.        大野欽司「神経領域のRNA病」細胞工学 29(2) 131-136, 2010.

5.        大野欽司「神経筋疾患におけるスプライシング異常」蛋白質 核酸 酵素 54(16): 2239-2244, 2009. PubMed

6.        大野欽司「先天性神経筋伝達分子欠損症とスプライシング異常」遺伝子医学MOOK 15 109-115, 2009.

7.        大野欽司、伊藤美佳子「タンパク質係留治療」生物の科学 遺伝63(5)： 97-102, 2009.

8.        大野欽司、伊藤美佳子、増田章男「プロトタイプシナプスとしての神経筋接合部の病態と治療戦略」日本神経精神薬理学雑誌 29(4): 145-151, 2009. PubMed

9.        大野欽司「スプライシングのゲノム解析」分子細胞治療 8(1): 58-63, 2009.

10.    松浦徹、大野欽司「SCA10」Clinical Neuroscience 27(1): 66-68, 2009.

11.    大野欽司、高橋昭（監訳）ヘインズ神経科学第３版・第２章「ニューロンとグリアの細胞生物学」pp 14-35・第３章「神経機能の電気化学的基礎」pp36-58・第4章「神経伝達の化学的基盤」pp59-73 エルセビアジャパン、東京、2008

12.    大野欽司「先天性筋無力症候群」Clinical Neuroscience 26 (9): 990-991, 2008.

13.    大野欽司「神経・筋疾患におけるRNA病態」臨床神経 47: 801-804, 2007. PubMed

14.    大野欽司「スプライシング異常と疾患」分子細胞治療 5: 393-399, 2006.

15.    松浦徹、大野欽司「SCA10の分子遺伝学」神経研究の進歩50: 339-346, 2006.

16.    松浦徹、大野欽司「非翻訳リピート病のRNA病態」メディカル・サイエンス・ダイジェスト32: 25-28, 2006.

17.    大野欽司、Engel AG. 「先天性筋無力症候群」神経眼科 22: 326-335, 2005.

18.    大野欽司、Andrew G. Engel、佐橋功「先天性筋無力症候群」Annual Review神経2003 :271-274, 2003.

19.    大野欽司、田中雅嗣、佐橋功「電子伝達フラビンタンパク質」日本臨牀60 (4), 113-117, 2002.

20.    大野欽司、田中雅嗣、佐橋功「幼児および小児の自己免疫性重症筋無力症」日本臨牀36: 340-343, 2001.

21.    大野欽司、Engel AG. 「先天性筋無力症候群」脳と神経 49:1102-1113, 1997.

22.    佐橋功、衣斐達、米田誠、田中雅嗣、大野欽司「ミトコンドリアDNAの転移RNA-Tyr変異に伴う慢性進行性外眼筋麻痺－臨床と分子細胞学的検討－」日本臨牀55: 3265-326, 1997.

23.    大野欽司、田中雅嗣「ミトコンドリア DNA」神経眼科11:4-13, 1994.

24.    大野欽司、小澤高将「ミトコンドリア電子伝達系欠損によるミオグロビン尿症─ミオグロビン尿症のあらたな病因の提唱─」医学のあゆみ160: 912, 1992.

25.    田代伯為、佐橋功、衣斐達、周防拡、大野欽司「Mitochondrial Encephalopathy, Lactic Acidosis and Stroke-like Episodes (MELAS)症候群─成人発症例の臨床筋病理分子遺伝学的検討─」神経眼科9: 331-338, 1992.

26.    衣斐達、佐橋功、田代伯為、周防拡、大野欽司「MNGIE 症候群－臨床特徴と分子遺伝学的検討－」神経眼科 9: 59-63, 1992.