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Unpublished Paper
Rapid Tumor Induction in Zebrafish by TALEN-Mediated Somatic Inactivation of the Retinoblastoma1 Tumor Suppressor rb1
Scientific Reports
  • Staci L. Solin, Iowa State University
  • Heather R. Shive, North Carolina State University at Raleigh
  • Kevin D. Woolard, University of California - Davis
  • Jeffrey J. Essner, Iowa State University
  • Maura McGrail, Iowa State University
Document Type
Article
Publication Version
Published Version
Publication Date
9-1-2015
DOI
10.1038/srep13745
Abstract

Investigating the in vivo role of tumor suppressor genes in cancer is technically challenging due to their essential requirement during early animal development. To address this bottleneck, we generated genetic mosaic adult zebrafish using TALEN genome editing and demonstrate somatic inactivation of the tumor suppressor retinoblastoma1 (rb1) induces tumorigenesis at high frequency. 11–33% of 1-cell stage embryos injected with TALEN mRNAs targeting rb1 exon 2 or 3 develop tumors beginning as early as 3.5 months of age. Lesions predominantly arise in the brain and show features of neuroectodermal-like and glial-like tumors. Mutant allele analysis is consistent with tumor initiation due to somatic inactivation of rb1, revealing a conserved role for rb1 in tumor suppression across vertebrates. In contrast to genetic mosaics, heterozygous rb1−/+ adults show no evidence of neoplasia, while homozygous mutant rb1−/− are larval lethal. This is the first demonstration that somatic inactivation of a tumor suppressor causes cancer in zebrafish, and highlights the utility of site-specific nucleases to create genetic mosaic zebrafish for tumor suppressor gene discovery. Somatic inactivation with site-directed nucleases in zebrafish presents a rapid and scalable strategy to study tumor suppressor gene function in cancer.

Comments

This article is from Scientific Reports 5 (2015): 13745, doi:10.1038/srep13745. Posted with permission.

Rights
This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Copyright Owner
Staci L. Solin, et al
Language
en
File Format
application/pdf
Citation Information
Staci L. Solin, Heather R. Shive, Kevin D. Woolard, Jeffrey J. Essner, et al.. "Rapid Tumor Induction in Zebrafish by TALEN-Mediated Somatic Inactivation of the Retinoblastoma1 Tumor Suppressor rb1" Scientific Reports Vol. 5 (2015) p. 1 - 9
Available at: http://works.bepress.com/jeffrey_essner/7/