Zebrafish models in translational research: tipping the scales toward advancements in human health

Phillips, Jennifer B.; Westerfield, Monte

doi:10.1242/dmm.015545

Cited by 166 publications

(120 citation statements)

References 74 publications

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“…Zebrafish excel as a model to uncover gene function (59,60) and are now advancing research in many fields, including stem cell biology (61,62), cancer (63,64), infectious disease (65,66), and autoimmune disease studies (67,68). In this context, we consider the identification of expressed genes in our zebrafish MHC assembly to be noteworthy.…”

Section: Discussionmentioning

confidence: 99%

Alternative haplotypes of antigen processing genes in zebrafish diverged early in vertebrate evolution

McConnell

Hernandez

Wcisel

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

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Antigen processing and presentation genes found within the MHC are among the most highly polymorphic genes of vertebrate genomes, providing populations with diverse immune responses to a wide array of pathogens. Here, we describe transcriptome, exome, and whole-genome sequencing of clonal zebrafish, uncovering the most extensive diversity within the antigen processing and presentation genes of any species yet examined. Our CG2 clonal zebrafish assembly provides genomic context within a remarkably divergent haplotype of the core MHC region on chromosome 19 for six expressed genes not found in the zebrafish reference genome: mhc1uga, proteasome-β 9b (psmb9b), psmb8f, and previously unknown genes psmb13b, tap2d, and tap2e. We identify ancient lineages for Psmb13 within a proteasome branch previously thought to be monomorphic and provide evidence of substantial lineage diversity within each of three major trifurcations of catalytic-type proteasome subunits in vertebrates: Psmb5/Psmb8/Psmb11, Psmb6/ Psmb9/Psmb12, and Psmb7/Psmb10/Psmb13. Strikingly, nearby tap2 and MHC class I genes also retain ancient sequence lineages, indicating that alternative lineages may have been preserved throughout the entire MHC pathway since early diversification of the adaptive immune system ∼500 Mya. Furthermore, polymorphisms within the three MHC pathway steps (antigen cleavage, transport, and presentation) are each predicted to alter peptide specificity. Lastly, comparative analysis shows that antigen processing gene diversity is far more extensive than previously realized (with ancient coelacanth psmb8 lineages, shark psmb13, and tap2t and psmb10 outside the teleost MHC), implying distinct immune functions and conserved roles in shaping MHC pathway evolution throughout vertebrates.comparative genomics | proteasome and TAP evolution | major histocompatibility | MHC class I pathway | CG2 clonal zebrafish

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Section: Discussionmentioning

confidence: 99%

Alternative haplotypes of antigen processing genes in zebrafish diverged early in vertebrate evolution

McConnell

Hernandez

Wcisel

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

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“…Of particular note is the use of zebrafish to identify the anti-arthritis drug leflunomide as a potential treatment for melanoma, which is now being tested in a Phase I/II clinical trial [3]. This demonstrates a sufficiently close relationship between zebrafish and human biology to support the continued use of zebrafish for compound testing and drug discovery.…”

Section: Introductionmentioning

confidence: 97%

“…These include the ability to generate and house large numbers of vertebrates relatively quickly, cheaply and in a small space, their transparency during development, the sophisticated genetic and phenotyping techniques available, their high level of biological relevance to humans, and the identification of developing zebrafish as a 'replacement model' to avoid the use of protected animals in experiments: this has been recently reviewed in detail elsewhere [1][2][3][4]. Of particular note is the use of zebrafish to identify the anti-arthritis drug leflunomide as a potential treatment for melanoma, which is now being tested in a Phase I/II clinical trial [3].…”

Section: Introductionmentioning

confidence: 99%

New Zebrafish Models of Neurodegeneration

Martín-Jiménez

Campanella

Russell

2015

Curr Neurol Neurosci Rep

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In modern biomedicine the increasing need to develop experimental models to further our understanding of disease conditions and delineate innovative treatments has found in the zebrafish (Danio rerio) an experimental model, and indeed a valuable asset, to close the gap between in vitro and in vivo assays. Translation of ideas at a faster pace is vital in the field of neurodegeneration, with the attempt to slow or prevent the dramatic impact on society's welfare being an essential priority. Our research group has pioneered the use of zebrafish to contribute to the quest for faster and improved understanding and treatment of neurodegeneration in concert with, and inspired by, many others who have primed the study of the zebrafish to understand and search for a cure for disorders of the nervous system. Aware of the many advantages this vertebrate model holds, here we present an update on the recent zebrafish models available to study neurodegeneration with the goal of stimulating further interest and increasing the number of diseases and applications for which they can be exploited.We shall do so by citing and commenting on recent break-throughs made possible via zebrafish, highlighting their benefits for the testing of therapeutics and dissecting of disease mechanisms.

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“…The combination of mutant strains and inducible, reversible transgenes enables genetic approaches that closely mimic levels of gene expression characteristic of human disease. Zebrafish are already having an impact on diseases such as melanoma and other cancers, tuberculosis, autism, and cardiovascular disease (Phillips and Westerfield 2014).…”

Section: Zebrafish Models For Human Diseasementioning

confidence: 99%

Learning to Fish with Genetics: A Primer on the Vertebrate ModelDanio rerio

et al. 2016

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In the last 30 years, the zebrafish has become a widely used model organism for research on vertebrate development and disease. Through a powerful combination of genetics and experimental embryology, significant inroads have been made into the regulation of embryonic axis formation, organogenesis, and the development of neural networks. Research with this model has also expanded into other areas, including the genetic regulation of aging, regeneration, and animal behavior. Zebrafish are a popular model because of the ease with which they can be maintained, their small size and low cost, the ability to obtain hundreds of embryos on a daily basis, and the accessibility, translucency, and rapidity of early developmental stages. This primer describes the swift progress of genetic approaches in zebrafish and highlights recent advances that have led to new insights into vertebrate biology.

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Zebrafish models in translational research: tipping the scales toward advancements in human health

Cited by 166 publications

References 74 publications

Alternative haplotypes of antigen processing genes in zebrafish diverged early in vertebrate evolution

Alternative haplotypes of antigen processing genes in zebrafish diverged early in vertebrate evolution

New Zebrafish Models of Neurodegeneration

Learning to Fish with Genetics: A Primer on the Vertebrate ModelDanio rerio

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