Skip to main content

p53-Deficient Medaka Created by TILLING

  • Chapter
Medaka

Abstract

Because loss-of-function experiments in medaka and zebrafish had relied on morpholino, whose effect is transient and lasts only a few days post fertilization, developmental biology has been the major target of research using these small laboratory fish. With the advent of targeting-induced local lesions in genome (TILLING) technology, the teleost has reemerged as a model animal in which the specific genes can be disrupted. The potential research field is now expanded to slow and time-consuming biological phenomena such as carcinogenesis, aging, and degeneration. p53 is a multifunctional transcription factor involved in such various biological processes. Among other vertebrates, medaka is especially suited for the TILLING approach because of the compact genome and inbred strains, which makes amplicon design and screening fast and efficient. We have generated several lines of p53 mutant medaka, including two nonsense mutants. These lines showed the impaired transcriptional regulation of the cell cycle and apoptosis and the increased incidence of spontaneous tumorigenesis. The mutant medaka isolated by TILLING will occupy an important and valuable position in various research fields in the future.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 169.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 219.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 219.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  • Aoki K, Matsudaira H (1977) Induction of hepatic tumors in a teleost (Oryzias latipes) after treatment with methylazoxymethanol acetate: brief communication. J Natl Cancer Inst 59:1747–1749

    PubMed  CAS  Google Scholar 

  • Berghmans S, Murphey RD, Wienholds E, Neuberg D, Kutok JL, Fletcher CD, Morris JP, Liu TX, Schulte-Merker S, Kanki JP, Plasterk R, Zon LI, Look AT (2005) tp53 Mutant zebrafish develop malignant peripheral nerve sheath tumors. Proc Natl Acad Sci USA 102:407–412

    Article  PubMed  CAS  Google Scholar 

  • Chen S, Hong Y, Scherer SJ, Schartl M (2001) Lack of ultraviolet-light inducibility of the medaka fish (Oryzias latipes) tumor suppressor gene p53. Gene (Amst) 264:197–203

    Article  CAS  Google Scholar 

  • Chen J, Ruan H, Ng SM, Gao C, Soo HM, Wu W, Zhang Z, Wen Z, Lane DP, Peng J (2005) Loss of function of def selectively up-regulates Delta113p53 expression to arrest expansion growth of digestive organs in zebrafish. Genes Dev 19:2900–2911

    Article  PubMed  CAS  Google Scholar 

  • Cho Y, Gorina S, Jeffrey PD, Pavletich NP (1994) Crystal structure of a p53 tumor suppressor-DNA complex: understanding tumorigenic mutations. Science 265:346–355

    Article  PubMed  CAS  Google Scholar 

  • Craig DW, Pearson JV, Szelinger S, Sekar A, Redman M, Corneveaux JJ, Pawlowski TL, Laub T, Nunn G, Stephan DA, Homer N, Huentelman MJ (2008) Identification of genetic variants using bar-coded multiplexed sequencing. Nat Methods 5:887–893

    Article  PubMed  CAS  Google Scholar 

  • Donehower LA, Harvey M, Slagle BL, McArthur MJ, Montgomery CA Jr, Butel JS, Bradley A (1992) Mice deficient for p53 are developmentally normal but susceptible to spontaneous tumours. Nature (Lond) 356:215–221

    Article  CAS  Google Scholar 

  • Doyon Y, McCammon JM, Miller JC, Faraji F, Ngo C, Katibah GE, Amora R, Hocking TD, Zhang L, Rebar EJ, Gregory PD, Urnov FD, Amacher SL (2008) Heritable targeted gene disruption in zebrafish using designed zinc-finger nucleases. Nat Biotechnol 26:702–708

    Article  PubMed  CAS  Google Scholar 

  • Feitsma H, Cuppen E (2008) Zebrafish as a cancer model. Mol Cancer Res 6:685–694

    Article  PubMed  CAS  Google Scholar 

  • Furutani-Seiki M, Sasado T, Morinaga C, Suwa H, Niwa K, Yoda H, Deguchi T, Hirose Y, Yasuoka A, Henrich T, Watanabe T, Iwanami N, Kitagawa D, Saito K, Asaka S, Osakada M, Kunimatsu S, Momoi A, Elmasri H, Winkler C, Ramialison M, Loosli F, Quiring R, Carl M, Grabher C, Winkler S, Del Bene F, Shinomiya A, Kota Y, Yamanaka T, Okamoto Y, Takahashi K, Todo T, Abe K, Takahama Y, Tanaka M, Mitani H, Katada T, Nishina H, Nakajima N, Wittbrodt J, Kondoh H (2004) A systematic genome-wide screen for mutations affecting organogenesis in medaka, Oryzias latipes. Mech Dev 121:647–658

    Article  PubMed  CAS  Google Scholar 

  • Harms K, Nozell S, Chen X (2004) The common and distinct target genes of the p53 family transcription factors. Cell Mol Life Sci 61:822–842

    Article  PubMed  CAS  Google Scholar 

  • Kasahara M, Naruse K, Sasaki S, Nakatani Y, Qu W, Ahsan B, Yamada T, Nagayasu Y, Doi K, Kasai Y, Jindo T, Kobayashi D, Shimada A, Toyoda A, Kuroki Y, Fujiyama A, Sasaki T, Shimizu A, Asakawa S, Shimizu N, Hashimoto S, Yang J, Lee Y, Matsushima K, Sugano S, Sakaizumi M, Narita T, Ohishi K, Haga S, Ohta F, Nomoto H, Nogata K, Morishita T, Endo T, Shin IT, Takeda H, Morishita S, Kohara Y (2007) The medaka draft genome and insights into vertebrate genome evolution. Nature (Lond) 447:714–719

    Article  CAS  Google Scholar 

  • Krause MK, Rhodes LD, Van Beneden RJ (1997) Cloning of the p53 tumor suppressor gene from the Japanese medaka (Oryzias latipes) and evaluation of mutational hotspots in MNNG-exposed fish. Gene (Amst) 189:101–106

    Article  CAS  Google Scholar 

  • Kruse JP, Gu W (2009) Modes of p53 regulation. Cell 137:609–622

    Article  PubMed  CAS  Google Scholar 

  • Li FP, Fraumeni JF Jr, Mulvihill JJ, Blattner WA, Dreyfus MG, Tucker MA, Miller RW (1988) A cancer family syndrome in twenty-four kindreds. Cancer Res 48:5358–5362

    PubMed  CAS  Google Scholar 

  • Masahito P, Aoki K, Egami N, Ishikawa T, Sugano H (1989) Life-span studies on spontaneous tumor development in the medaka (Oryzias latipes). Jpn J Cancer Res 80:1058–1065

    Article  PubMed  CAS  Google Scholar 

  • Meng X, Noyes MB, Zhu LJ, Lawson ND, Wolfe SA (2008) Targeted gene inactivation in zebrafish using engineered zinc-finger nucleases. Nat Biotechnol 26:695–701

    Article  PubMed  CAS  Google Scholar 

  • Moens CB, Donn TM, Wolf-Saxon ER, Ma TP (2008) Reverse genetics in zebrafish by TILLING. Brief Funct Genomic Proteomic 7:454–459

    Article  PubMed  CAS  Google Scholar 

  • Taniguchi Y, Takeda S, Furutani-Seiki M, Kamei Y, Todo T, Sasado T, Deguchi T, Kondoh H, Mudde J, Yamazoe M, Hidaka M, Mitani H, Toyoda A, Sakaki Y, Plasterk RH, Cuppen E (2006) Generation of medaka gene knockout models by target-selected mutagenesis. Genome Biol 7:R116

    Article  PubMed  Google Scholar 

  • Vousden KH, Prives C (2009) Blinded by the light: the growing complexity of p53. Cell 137:413–431

    Article  PubMed  CAS  Google Scholar 

  • Winkler C, Wittbrodt J, Lammers R, Ullrich A, Schartl M (1994) Ligand-dependent tumor induction in medakafish embryos by a Xmrk receptor tyrosine kinase transgene. Oncogene 9:1517–1525

    PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Yoshihito Taniguchi .

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2011 Springer

About this chapter

Cite this chapter

Taniguchi, Y. (2011). p53-Deficient Medaka Created by TILLING. In: Naruse, K., Tanaka, M., Takeda, H. (eds) Medaka. Springer, Tokyo. https://doi.org/10.1007/978-4-431-92691-7_10

Download citation

Publish with us

Policies and ethics