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Development of cynomolgus monkey with hereditary retinal diseases

Research Project

Project/Area Number 26670762
Research Category

Grant-in-Aid for Challenging Exploratory Research

Allocation TypeMulti-year Fund
Research Field Ophthalmology
Research Institution独立行政法人国立病院機構(東京医療センター臨床研究センター)

Principal Investigator

IWATA Takeshi  独立行政法人国立病院機構(東京医療センター臨床研究センター), 分子細胞生物学研究部, 部長 (90374157)

Co-Investigator(Kenkyū-buntansha) MIZOTA Atsushi  帝京大学, 医学部, 教授 (10239262)
SHIMOZAWA Nobuhiro  医薬基盤研究所, 霊長類医科学研究センター, 主任研究員 (50300786)
Project Period (FY) 2014-04-01 – 2015-03-31
Project Status Completed (Fiscal Year 2014)
Budget Amount *help
¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000)
Fiscal Year 2014: ¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000)
Keywords外科系臨床医学 / 眼科学 / 眼生化学・分子生物学 / カニクイザル / 医歯薬学
Outline of Final Research Achievements

Number of hereditary retinal diseases in human is related to photoreceptors in the macula. The primate has unique structural and functional characteristic, which often becomes a problem using mouse or fish model of human retinal diseases. In this study, CRISPR/Cas9 was used to specifically cut the genome DNA in the fertilized egg to develop gene manipulated cynomolgus monkeys with hereditary retinal diseases. The fertilized egg was injected at the nucleus with CRISPR/Cas9 DNA vector and both in vitro culture and embryo transplantation was performed. ES cells were detected with DNA cleavage at the site targeted. However, one new born monkey derived from injected fertilized egg did not carry the mutation suggesting the germ line mutation was not achieved. The detection of targeted mutation in ES cells provides the possibility of new born mutation by continuation of further experiments. New methods of CRISPR/Cas9 will be tried to increase the efficiency of specific genome DNA cleavage.

Report

(2 results)
  • 2014 Annual Research Report   Final Research Report ( PDF )
  • Research Products

    (11 results)

All 2015 2014

All Journal Article (11 results) (of which Peer Reviewed: 11 results,  Acknowledgement Compliant: 5 results,  Open Access: 4 results)

  • [Journal Article] High-Temperature Requirement A Serine Peptidase 1 Gene is Transcriptionally Regulated by Insertion/Deletion Nucleotides Located at the 3 Prime End of Age-Related Maculopathy Susceptibility 2 Gene in Patients with Age-Related Macular Degeneration.2015

    • Author(s)
      Iejima D, Itabashi T, Kawamura Y, Noda T, Yuasa S, Fukuda K, Oka C, Iwata T.
    • Journal Title

      The Journal of Biological Chemistry

      Volume: 290 Issue: 5 Pages: 2784-2797

    • DOI

      10.1074/jbc.m114.593384

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Novel nonsense and splice site mutations in CRB1 gene in two Japanese patients with early-onset retinal dystrophy Documenta Ophthalmologica.2015

    • Author(s)
      Kuniyoshi K, Ikeo K, Sakuramoto H, Furuno M, Yoshitake K, Hatsukawa Y, Nakao A, Kusaka S, Shimomura Y, Iwata T.
    • Journal Title

      Documenta Ophthalmologica

      Volume: 130 Issue: 1 Pages: 49-55

    • DOI

      10.1007/s10633-014-9464-8

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Lack of association of LOXL1 gene variants in Japanese patients with central retinal vein occlusion without clinically detectable pseudoexfoliation material deposits.2014

    • Author(s)
      Tanito M, Hara K, Akahori M, Harata A, Itabashi T, Takai Y, Kaidzu S, Ohira A, Iwata T.
    • Journal Title

      Acta Ophthalmologica

      Volume: 印刷確定 Issue: 3

    • DOI

      10.1111/aos.12534

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed
  • [Journal Article] RHO mutations (p.W126L and p.A346P) in two Japanese families with autosomal dominant retinitis pigmentosa2014

    • Author(s)
      Katagiri S, Hayashi T, Akahori M, Itabashi T, Nishio J, Yoshitake K, Furuno M, Ikeo K, Okada T, Tsuneoka H, Iwata T
    • Journal Title

      J Ophthalmol

      Volume: 2014 Pages: 210947-210947

    • DOI

      10.1155/2014/210947

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] RPE65 mutations in two Japanese families with Leber congenital amaurosis.2014

    • Author(s)
      Katagiri S, Hayashi T, Yoshitake K, Akahori M, Ikeo K, Gekka T, Tsuneoka H, Iwata T.
    • Journal Title

      Ophthalmic Genetics

      Volume: 12 Pages: 1-9

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Heterozygote Wdr36-deficient mice do not develop glaucoma.2014

    • Author(s)
      Gallenberger M, Kroeber M, Koch M, März L, Fuchshofer R, Iwata T, Braunger BM, Tamm ER.
    • Journal Title

      Experimental Eye Research

      Volume: 128 Pages: 83-91

    • DOI

      10.1016/j.exer.2014.09.008

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Overexpression of HtrA1 and exposure to mainstream cigarette smoke leads to choroidal neovascularization and subretinal deposits in aged mice2014

    • Author(s)
      Mao Nakayama, Daisuke Iejima, Masakazu Akahori, Junzo Kamei, Asako Goto, Takeshi Iwata
    • Journal Title

      IOVS (investigative ophthalmology&visual science)

      Volume: 55 Issue: 10 Pages: 6514-6523

    • DOI

      10.1167/iovs.14-14453

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Whole exome analysis identifies frequent CNGA1 mutations in Japanese population with autosomal recessive retinitis pigmentosa2014

    • Author(s)
      Katagiri S, Akahori M, Sergeev Y, Yoshitake K, Ikeo K, Furuno M, Hayashi T, Kondo M, Ueno S, Tsunoda K, Shinoda K, Kuniyoshi K, Tsurusaki Y, Matsumoto N, Tsuneoka H, Iwata T.
    • Journal Title

      Plos One

      Volume: 9(9) Issue: 9 Pages: e108721-e108721

    • DOI

      10.1371/journal.pone.0108721

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Novel C8orf37 mutations in patients with early-onset retinal dystrophy, macular atrophy, cataracts, and high myopia.2014

    • Author(s)
      Katagiri S, Hayashi T, Yoshitake K, Akahori M, Ikeo K, Gekka T, Tsuneoka H, Iwata T.
    • Journal Title

      Ophthalmic Genetics

      Volume: 12 Pages: 1-8

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Pattern visual evoked potentials elicited by organic electroluminescence screen.2014

    • Author(s)
      Matsumoto CS, Shinoda K, Matsumoto H, Funada H, Sasaki K, Minoda H, Iwata T, Mizota A.
    • Journal Title

      Biomed Res Int.

      Volume: 606951 Pages: 1-6

    • DOI

      10.1155/2014/606951

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Binocular interaction of visually evoked cortical potentials elicited by dichoptic binocular stimulation.2014

    • Author(s)
      Matsumoto CS, Nakagomi R, Matsumoto H, Minoda H, Shinoda K, Iwata T, Mizota A.
    • Journal Title

      J Vis.

      Volume: 14(11) Issue: 11 Pages: 1-9

    • DOI

      10.1167/14.11.4

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant

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Published: 2014-04-04   Modified: 2016-06-03  

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