Zebrafish As a Genetic Model in Pre-Clinical Drug Testing and Screening

Gibert, Yann; Trengove, Monique C.; Ward, Alister C.

doi:10.2174/0929867311320190005

Cited by 59 publications

(31 citation statements)

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“…Clearly, zebrafish also provides an inexpensive whole-animal vertebrate model for screening a library of small molecules, cell-or tissue receptorspecific compounds against viral pathogens or anti-angiogenic or anti-inflammatory compounds. 24,[46][47][48][49] One study has already employed this model to confirm the antiviral effect of acyclovir using HSV-1 infected zebrafish. 21 Ideally, zebrafish in a 96-well format can be treated with antibodies 50 or compounds targeting specific cells/tissues or modified antiviral peptides with an objective to have higher efficacy.…”

Section: Zebrafish Model: Overall Advantages To Study Viral Infectionsmentioning

confidence: 99%

Zebrafish: Modeling for Herpes Simplex Virus Infections

et al. 2014

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For many years, zebrafish have been the prototypical model for studies in developmental biology. In recent years, zebrafish has emerged as a powerful model system to study infectious diseases, including viral infections. Experiments conducted with herpes simplex virus type-1 in adult zebrafish or in embryo models are encouraging as they establish proof of concept with viral-host tropism and possible screening of antiviral compounds. In addition, the presence of human homologs of viral entry receptors in zebrafish such as 3-O sulfated heparan sulfate, nectins, and tumor necrosis factor receptor superfamily member 14-like receptor bring strong rationale for virologists to test their in vivo significance in viral entry in a zebrafish model and compare the structure-function basis of virus zebrafish receptor interaction for viral entry. On the other end, a zebrafish model is already being used for studying inflammation and angiogenesis, with or without genetic manipulations, and therefore can be exploited to study viral infection-associated pathologies. The major advantage with zebrafish is low cost, easy breeding and maintenance, rapid lifecycle, and a transparent nature, which allows visualizing dissemination of fluorescently labeled virus infection in real time either at a localized region or the whole body. Further, the availability of multiple transgenic lines that express fluorescently tagged immune cells for in vivo imaging of virus infected animals is extremely attractive. In addition, a fully developed immune system and potential for receptor-specific knockouts further advocate the use of zebrafish as a new tool to study viral infections. In this review, we focus on expanding the potential of zebrafish model system in understanding human infectious diseases and future benefits.

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Section: Zebrafish Model: Overall Advantages To Study Viral Infectionsmentioning

confidence: 99%

Zebrafish: Modeling for Herpes Simplex Virus Infections

et al. 2014

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“…The extra-uterine development of hundreds of eggs also permits a greater number of studies in genetically identical organisms. Since the first reported xenotransplantation of human cells into zebrafish ( Lee et al , 2005), many laboratories have shown that zebrafish embryos are useful for the study of other facets of tumour biology including cancer-induced angiogenesis ( Haldi et al , 2006); cancer cell invasion and metastasis ( de Boeck et al , 2016; Marques et al , 2009); cancer stem cell growth ( Bansal et al , 2014; Chen et al , 2017); interaction of cancer cells with the host ( Feng & Martin, 2015); and drug screening ( Corkery et al , 2011; Gibert et al , 2013). Importantly, the development of human tumours and their response to chemotherapeutic treatment in zebrafish embryos is comparable to that observed in mouse xenograft assays ( Fior et al , 2017).…”

Section: Introductionmentioning

confidence: 99%

Embryonic zebrafish xenograft assay of human cancer metastasis

et al. 2018

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Cancer metastasis is the most important prognostic factor determining patient survival, but currently there are very few drugs or therapies that specifically inhibit the invasion and metastasis of cancer cells. Currently, human cancer metastasis is largely studied using transgenic and immunocompromised mouse xenograft models, which are useful for analysing end-point tumour growth but are unable to accurately and reliably monitor in vivo invasion, intravasation, extravasation or secondary tumour formation of human cancer cells. Furthermore, limits in our ability to accurately monitor early stages of tumour growth and detect micro-metastases likely results in pain and suffering to the mice used for cancer xenograft experiments. Zebrafish ( Danio rerio) embryos, however, offer many advantages as a model system for studying the complex, multi-step processes involved during cancer metastasis. This article describes a detailed method for the analysis of human cancer cell invasion and metastasis in zebrafish embryos before they reach protected status at 5 days post fertilisation. Results demonstrate that human cancer cells actively invade within a zebrafish microenvironment, and form metastatic tumours at secondary tissue sites, suggesting that the mechanisms involved during the different stages of metastasis are conserved between humans and zebrafish, supporting the use of zebrafish embryos as a viable model of human cancer metastasis. We suggest that the embryonic zebrafish xenograft model of human cancer is a tractable laboratory model that can be used to understand cancer biology, and as a direct replacement of mice for the analysis of drugs that target cancer invasion and metastasis.

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“…The average length of an adult fish is at 2 to 4 cm, accessible for relatively low-cost and high-throughput small molecule screening[9]. Their physiological complexity also provides conserved models of human disease for in vivo validation studies[10].…”

Section: Introductionmentioning

confidence: 99%

Flexible and waterproof micro-sensors to uncover zebrafish circadian rhythms: The next generation of cardiac monitoring for drug screening

Zhang

Beebe²,

Jen³

et al. 2015

Biosensors and Bioelectronics

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Flexible electronics are the next generation of sensors for mobile health and implantation. Zebrafish (Danio rerio) is an emergent strategy for pre-clinical drug development and toxicity testing. To address the confounding effects from sedation of fish and removal from the aquatic habitat for micro-electrocardiogram (μECG) measurements, we developed waterproof and wearable sensors to uncover the circadian variation in heart rate (HR) and heart rate variability (HRV)[1]. The parylene-C based ECG sensor consisted of an ultra-soft silicone integrated jacket designed to wrap around the fish during swimming. The Young’s modulus of this silicone jacket matched with the fish surface, and an extended parylene cable connected the underwater chest electrodes with the out-of water electronics. In addition, embedded micro-glass spheres in the silicone effectively reduced the effective density of the jacket to ~ 1 g·cm−3. These innovations enabled physiological ECG telemetry in the fish’s natural habitat without the need for sedation. Furthermore, a set of non-linear signal processing techniques filtered out the breathing and electromagnetic artifacts from the recorded signals. We observed a reduction in mean HR and an increase in HRV over 24 hours at 10 dpa, accompanied by QT prolongation as well as diurnal variations, followed by normalization in mean HR and QT intervals at 26 days post ventricular amputation (dpa). We revealed Amiodarone-mediated QTc prolongation, HR reduction and HRV increase otherwise masked by sedation. The novel features of the flexible silicon jacket for μECG telemetry unraveled the biological clock and normalization of QT intervals at 26 dpa, providing the first evidence of new physiological phenomena during cardiac injury and repair as well as cardiac drug-mediated aberrant rhythms. Thus, the light weight and waterproof design holds promise to advance the next generation of mobile health and drug discovery.

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Zebrafish As a Genetic Model in Pre-Clinical Drug Testing and Screening

Cited by 59 publications

References 0 publications

Zebrafish: Modeling for Herpes Simplex Virus Infections

Zebrafish: Modeling for Herpes Simplex Virus Infections

Embryonic zebrafish xenograft assay of human cancer metastasis

Flexible and waterproof micro-sensors to uncover zebrafish circadian rhythms: The next generation of cardiac monitoring for drug screening

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