Development of a premature aging syndrome non-human primate model

• Project/Area Number: 26640053
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Laboratory animal science
• Research Institution: Shiga University of Medical Science
• Principal Investigator: Itoh Yasushi 滋賀医科大学, 医学部, 准教授 (90324566)
• Co-Investigator(Kenkyū-buntansha): 土屋 英明 滋賀医科大学, 動物生命科学研究センター, 技術専門職員 (10378440) ; 佐々木 えりか 公益財団法人実験動物中央研究所, 応用発生学研究センター, センター長 (70390739) ; 依馬 正次 滋賀医科大学, 動物生命科学研究センター, 教授 (60359578) ; 小笠原 一誠 滋賀医科大学, 医学部, 教授 (20169163)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000); Fiscal Year 2016: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000); Fiscal Year 2015: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2014: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
• Keywords: 老化 / 癌 / トランスレーショナルリサーチ / 病理学 / 霊長類モデル / ゲノム編集 / レンチウイルスベクター / 遺伝子編集

Outline of Final Research Achievements

We established genetically modified cynomolgus monkeys to reveal pathogenicity of a premature aging syndrome. Using a lentivirus vector, we obtained cynomolgus macaques that express GFP in the whole body. Next, we made plasmid vectors to examine gene modification in the cultured cells of cynomolgus macaques using CRISPR/Cas9 genome editing technology. We confirmed the high efficiency of genome editing in the Werner DNA helicase gene with the CRISPR/Cas9 system in vitro. Thereafter, using the CRISPR/Cas9 system and in vitro microfertilization, we have obtained a cynomolgus macaque that carries gene mutation in the Werner DNA helices gene. We continue observation of this macaque and examination of disease pathogenesis.

Research Products

• [Journal Article] Potential Risk of Repeated Nasal Vaccination that Induces Allergic Reaction with Mucosal IgE and Airway Eosinophilic Infiltration in Cynomolgus Macaques infected with H5N1 Highly Pathogenic Avian Influenza Virus (2017)
  • Author(s): Nakayama M, Itoh Y, Shichinohe S, Nakabayashi R, Ishigaki H, Sakoda Y, Le QM, Kawaoka Y, Kida H, Ogasawara K
  • Journal Title: Vaccine Volume: 35 Pages: 1008-1017
  • Peer Reviewed / Open Access
• [Journal Article] Vaccination against H9N2 avian influenza virus reduces bronchus-associated lymphoid tissue formation in cynomolgus macaques after intranasal virus challenge infection (2016)
  • Author(s): Nakayama M, Ozaki H, Itoh Y, Soda K, Ishigaki H, Okamatsu M, Sakoda Y, Park C-H, Tsuchiya H, Kida H, Ogasawara K
  • Journal Title: Pathology International Volume: 66 Issue: 12 Pages: 678-686
  • DOI: 10.1111/pin.12472
  • Peer Reviewed
• [Journal Article] Surgical technique for allogeneic uterus transplantation in macaques (2016)
  • Author(s): Obara H, Kisu I, Kato Y, Yamada Y, Matsubara K, Emoto K, Adachi M, Matoba Y, Umene K, Nogami Y, Banno K, Tsuchiya H, Itagaki I, Kawamoto I, Nakagawa T, Ishigak Hi, Itoh Y, Ogasawara K, Saiki Y, Sato S-i, Nakagawa N, Shiina T, Aoki D, Kitagawa Y
  • Journal Title: Scientific Reports Volume: 6 Issue: 1 Pages: 35989-35989
  • DOI: 10.1038/srep35989
  • Peer Reviewed / Open Access
• [Journal Article] Sensitization with vaccinia virus harboring hemagglutinin recovers the immune potential against highly pathogenic H5N1 influenza virus in non-human primates (2016)
  • Author(s): Fumihiko Yasui, Yasushi Itoh, Ai Ikejiri, Masahiro Kitabatake, Nobuo Sakaguchi, Keisuke Munekata, Shintaro Shichinohe, Yukiko Hayashi, Hirohito Ishigaki, Misako Nakayama, Yoshihiro Sakoda, Hiroshi Kida, Kazumasa Ogasawara, *Michinori Kohara
  • Journal Title: Scientific Reports Volume: 6 Issue: 1 Pages: 37915-37915
  • DOI: 10.1038/srep37915
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Generation of transgenic cynomolgus monkeys that express green fluorescent protein throughout the whole body (2016)
  • Author(s): Seita Y, Tsukiyama T, Iwatani C, Tsuchiya H, Matsushita J, Azami T, Okahara J, Nakamura S, Hayashi Y, Hitoshi S, Itoh Y, Imamura T, Nishimura M, Tooyama I, Miyoshi H, Saitou M, Ogasawara K, Sasaki E, Ema M
  • Journal Title: Scientific Reports Volume: 2 Issue: 1 Pages: 24868-24868
  • DOI: 10.1038/srep24868
  • NAID: 130007023590
  • Peer Reviewed / Open Access
• [Journal Article] Comparison of pathogenicities of H7 avian influenza viruses via intranasal and conjunctival inoculation in cynomolgus macaques (2016)
  • Author(s): Shichnohe S, Itoh Y, Nakayama M, Ozaki H, Soda K, Ishigaki H, Okamatsu M, Sakoda Y, Kida H, Ogasawara K
  • Journal Title: Virology Volume: 493 Pages: 31-38
  • DOI: 10.1016/j.virol.2016.03.007
  • Peer Reviewed
• [Journal Article] Translational research on influenza virus infection using a nonhuman primate model (2016)
  • Author(s): Itoh Y
  • Journal Title: Pathology International Volume: 66 Issue: 3 Pages: 132-141
  • DOI: 10.1111/pin.12385
  • Peer Reviewed
• [Journal Article] Efficacy of repeated intravenous administration of peramivir against highly pathogenic avian influenza A (H5N1) virus in cynomolgus macaques. (2014)
  • Author(s): Kitano M, Itoh Y, Ishigaki H, Nakayama M, Ishida H, Pham VL, Arikata M, Shichinohe S, Tsuchiya H, Kitagawa N, Kobayashi M, Yoshida R, Sato A, Le QM, Kawaoka Y, Ogasawara K
  • Journal Title: Antimicrobial Agents and Chemotherapy Volume: 58 Issue: 8 Pages: 4795-4803
  • DOI: 10.1128/aac.02817-14
  • Peer Reviewed / Open Access
• [Journal Article] The zoonotic potential of avian influenza viruses isolated from wild waterfowl in Zambia (2014)
  • Author(s): Simulundu E, Nao N, Yabe J, Muto NA, Sithebe T, Sawa H, Manzoor R, Kajihara M, Muramatsu M, Ishii A, Ogawa H, Mweene AS, Takada A
  • Journal Title: Arch. Virol. Volume: 159 Issue: 6 Pages: 2633-2640
  • DOI: 10.1371/journal.ppat.1004192
  • NAID: 120005656330
  • Peer Reviewed / Open Access
• [Journal Article] Disease severity is associated with differential gene expression at the early and late phases of infection in nonhuman primates infected with different H5N1 highly pathogenic avian influenza viruses. (2014)
  • Author(s): Muramoto Y, Shoemaker JE, Le MQ, Itoh Y, Tamura D, Sakai-Tagawa Y, Imai H, Uraki R, Takano R, Kawakami E, Ito M, Okamoto K, Ishigaki H, Mimuro H, Sasakawa C, Matsuoka Y, Noda T, Fukuyama S, Ogasawara K, Kitano H, Kawaoka Y.
  • Journal Title: Journal of Virlogy Volume: 88(16) Issue: 16 Pages: 8981-8997
  • DOI: 10.1128/jvi.00907-14
  • Peer Reviewed / Open Access
• [Presentation] 霊長類モデルを用いたインフルエンザウイルスの病原性の解明と予防・治療法の開発 (2014)
  • Author(s): 伊藤 靖
  • Organizer: 第６０回日本病理学会秋期特別総会
  • Place of Presentation: 国立劇場おきなわ（沖縄県浦添市）
  • Year and Date: 2014-11-21
• [Remarks] 本研究室より発表した論文の紹介
  • URL: http://www.shiga-med.ac.jp/~hqpatho2/publications.html
• [Remarks] 重点研究プロジェクト
  • URL: https://www.shiga-med.ac.jp/research-and-collaboration/priority-projects-and-research-results
• [Remarks] 本研究室より発表した論文の紹介
  • URL: http://www.shiga-med.ac.jp/~hqpatho2/journal_club.html