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Hooked! Modeling human disease in zebrafish
Cristina Santoriello, Leonard I. Zon
Cristina Santoriello, Leonard I. Zon
Published July 2, 2012
Citation Information: J Clin Invest. 2012;122(7):2337-2343. https://doi.org/10.1172/JCI60434.
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Science in Medicine

Hooked! Modeling human disease in zebrafish

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Abstract

Zebrafish have been widely used as a model system for studying developmental processes, but in the last decade, they have also emerged as a valuable system for modeling human disease. The development and function of zebrafish organs are strikingly similar to those of humans, and the ease of creating mutant or transgenic fish has facilitated the generation of disease models. Here, we highlight the use of zebrafish for defining disease pathways and for discovering new therapies.

Authors

Cristina Santoriello, Leonard I. Zon

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Figure 3

Reverse genetic approaches to generating zebrafish disease models.

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Reverse genetic approaches to generating zebrafish disease models.
(A) M...
(A) Morpholinos or mRNA are injected into embryos to transiently knock down or overexpress a potential disease gene. Phenotypic analysis is performed on these embryos. Alternatively, mRNA encoding ZFN or TALEN is injected into the embryos. Putative founders are raised to adulthood and outcrossed to identify carriers. Founders carrying the allele of interest are then outcrossed to generate an F1 population. Heterozygous F1 carriers are identified by genotyping. (B) TILLING: adult males that have been mutagenized by treatment with ENU are crossed to wild-type females. A DNA library of tailfin clips or frozen sperm is prepared from F1 males. PCR amplification of exons of a specific gene of interest followed by sequencing is performed on the genomic library. Once a mutation is identified, the fish carrying the mutation will be recovered by crossing the corresponding fish from the live library to a wild-type fish or by thawing the cryopreserved sperm and using it for in vitro fertilization (IVF). The resulting progeny are then intercrossed to generate heterozygous and homozygous mutants for the disease gene.

Copyright © 2025 American Society for Clinical Investigation
ISSN: 0021-9738 (print), 1558-8238 (online)

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