Abstract
Zebrafish are rapidly becoming a leading model organism for cancer research. The genetic pathways driving cancer are highly conserved between zebrafish and humans, and the ability to easily manipulate the zebrafish genome to rapidly generate transgenic animals makes zebrafish an excellent model organism. Transgenic zebrafish containing complex, patient-relevant genotypes have been used to model many cancer types. Here we present a comprehensive review of transgenic zebrafish cancer models as a resource to the field and highlight important areas of cancer biology that have yet to be studied in the fish. The ability to image cancer cells and niche biology in an endogenous tumor makes zebrafish an indispensable model organism in which we can further understand the mechanisms that drive tumorigenesis and screen for potential new cancer therapies.
Highlights
Zebrafish (Danio rerio) share 70% of their genome with humans and are commonly used to model human disease (Howe et al 2013)
Zebrafish expressing both Notch and Myc have more aggressive T-Acute lymphoblastic leukemia (ALL), and TOX was identified as an oncogene that synergized with MYC and NOTCH1 to accelerate T cell ALL (T-ALL) by expanding transformed clones and increasing genomic instability (Blackburn et al 2012, Lobbardi et al 2017)
Zebrafish models of sarcomas, including rhabdomyosarcoma, chordoma, hemangiosarcoma, and liposarcoma, have been extensively reviewed, so here we focus on common transgenic models in zebrafish (Hayes & Langenau 2017)
Summary
Zebrafish (Danio rerio) share 70% of their genome with humans and are commonly used to model human disease (Howe et al 2013). Adult zebrafish can be used for drug screening as well; it can be difficult to administer the concentration of the drug necessary exclusively in their water. Techniques such as oral gavage, intraperitoneal injection, and retro-orbital injection have been developed to address this problem (Dang et al 2016, Kinkel et al 2010, Pugach et al 2009). Systems for perturbing candidate genes are readily available in the zebrafish, via either overexpression in a DNA transposon system, knockdown using morpholinos, or knockout with CRISPR (clustered regularly interspaced short palindromic repeats)/Cas. Melanocyte development is conserved between zebrafish and mammals, making zebrafish excellent models of pigmentation and melanoma (Mort et al 2015). Expression of human BRAFV600E, under the melanocyte-specific mitfa promoter, leads to formation of melanocytic nevi (moles), but Neuroblastoma
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