title: Approaches to Inactivate Genes in Zebrafish.
abstract: Animal models of tumor initiation and tumor progression are essential components toward understanding cancer and designing/validating future therapies. Zebrafish is a powerful model for studying tumorigenesis and has been successfully exploited in drug discovery. According to the zebrafish reference genome, 82 % of disease-associated genes in the Online Mendelian Inheritance in Man (OMIM) database have clear zebrafish orthologues. Using a variety of large-scale random mutagenesis methods developed to date, zebrafish can provide a unique opportunity to identify gene mutations that may be associated with cancer predisposition. On the other hand, newer technologies enabling targeted mutagenesis can facilitate reverse cancer genetic studies and open the door for complex genetic analysis of tumorigenesis. In this chapter, we will describe the various technologies for conducting genome editing in zebrafish with special emphasis on the approaches to inactivate genes.
authors.affiliation: Department of Pharmacology and Toxicology, UAB Comprehensive Cancer Center, University of Alabama at Birmingham School of Medicine, Birmingham, AL, 35294, USA. jparant@uab.edu.
authors.forename: John M
authors.initials: JM
authors.lastname: Parant
authors.affiliation: Cardiovascular Research Center, Massachusetts General Hospital, Charlestown, MA, 02129, USA. jyeh1@mgh.harvard.edu.|Department of Medicine, Harvard Medical School, Boston, MA, 02115, USA. jyeh1@mgh.harvard.edu.
authors.forename: Jing-Ruey Joanna
authors.initials: JR
authors.lastname: Yeh
mesh_terms: D000818:Animals; D064112:Clustered Regularly Interspaced Short Palindromic Repeats; D004195:Disease Models, Animal; D016296:Mutagenesis; D009369:Neoplasms / Q000235:genetics*; D012190:Retroviridae / Q000235:genetics; D019076:Transgenes; D015027:Zebrafish
keywords: CRISPR; Cancer; Cas9; Gene targeting; Genome engineering; Homologous recombination; Mutagenesis; Transcription activator-like effector nuclease; Zebrafish; Zinc finger nuclease