Generation of a new mouse model of inducible rod photoreceptor degeneration

• Project/Area Number: 24791840
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Ophthalmology
• Research Institution: The University of Tokyo
• Principal Investigator: KOSO Hideto 東京大学, 医科学研究所, 特任助教 (50612876)
• Project Period (FY): 2012-04-01 – 2014-03-31
• Project Status: Completed (Fiscal Year 2013)
• Budget Amount: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000); Fiscal Year 2013: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000); Fiscal Year 2012: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
• Keywords: 網膜変性 / マウス / モデルマウス / 網膜 / 視細胞 / 変性 / グリア / 再生

Research Abstract

Retinitis pigmentosa and macular degeneration are characterized by progressive degeneration of photoreceptor cells. There are still no effective treatments to cure these diseases. Recent studies have shown that Muller glia, the most abundant glia in the retina, de-differentiate upon injury, and regenerate neurons. To identify drugs that promote the regenerative potential of Muller glia, it is essential to establish an in vitro model of photoreceptor degeneration. By using genetically engineered mice, I generated a new mouse model of photoreceptor degeneration. Retinal explant culture experiments showed that photoreceptor degeneration and Muller glial activation could be induced by tamoxifen-dependent recombination in vitro. To my knowledge, this is the first in vitro model of photoreceptor degeneration and Muller glial activation that can be induced in a temporally controlled manner. This model facilitates the discovery of drugs that promote the regenerative potential of Muller glia.

Research Products

• [Journal Article] Profiling of MicroRNA in Human and Mouse ES and iPS Cells Reveals Overlapping but Distinct MicroRNA Expression Patterns. (2013)
  • Author(s): Razak SR, Ueno K, Takayama N, Nariai N, Nagasaki M, Saito R, Koso H, Lai CY, Murakami M, Tsuji K, Michiue T, Nakauchi H, Otsu M, Watanabe S.
  • Journal Title: PLoS One. Volume: 8 Issue: 9 Pages: e73532-e73532
  • DOI: 10.1371/journal.pone.0073532
  • Peer Reviewed / Open Access
• [Journal Article] Musashi-CreERT2 : A new cre line for conditional mutagenesis in neural stem cells (2013)
  • Author(s): Takeda H, Koso H, Tessarollo L, Copeland NG, Jenkins NA
  • Journal Title: Genesis Volume: 51 (2) Issue: 2 Pages: 128-34
  • DOI: 10.1002/dvg.22357
  • Peer Reviewed
• [Journal Article] Transposon mutagenesis identifies genes that transform neural stem cells into glioma-initiating cells (2012)
  • Author(s): Koso Hideto
  • Journal Title: Proc Natl Acad Sci U S A Volume: 109 Issue: 44 Pages: 2998-3007
  • DOI: 10.1073/pnas.1215899109
  • Peer Reviewed
• [Remarks]
  • URL: http://www.ims.u-tokyo.ac.jp/moldev/
• [Remarks] 研究室のホームページ（研究内容が記載）
  • URL: http://www.ims.u-tokyo.ac.jp/moldev/