potential application of zebrafish in research

Although no animal can perfectly model a human disease, I believe these little striped swimmers have great potential for advancing medical research in the future. Introduction: The use of zebrafish (Danio rerio) larvae was investigated to predict adverse visual effects and to establish the potential application of this organism in early drug safety assessment. In vitro fertilization can be performed if necessary. Zebrafish constitutes an ideal model for this study since 1) they undergo rapid development, accomplishing primary organogenesis within 48 h post fertilization, 2) their ex utero development greatly facilitates monitoring abnormalities and examination of temporal windows of sensitivity to a stressor 3) RFR exposures of hundreds of embryos can be done uniformly in a multi-well plate inside a small … But, there are also purely scientific reasons why ‘lower’ organisms, such as zebrafish, can create a better model system. This figure shows visual differences in muscle between wild-type zebrafish larva (A, B, C) and distrophic larva (A’, B’, C’). 2016).The embryonic zebrafish model has been used for this purpose in pharmaceutical development and in high-throughput screening programs at NTP … Biomedical researchers are taking advantage of the vast amount of genetic information available in public databases, and in medical records, to explore the causes of human disease and gain insight to help the development of novel, as well as personalised, treatments. A recent study conducted by the University of Alberta suggests that the cannabis compounds THC and CBD may have negative effects on the development of the nervous system. Recently, Zebrafish has sparked interest in other branches of the biomedical research because of its emerging potential for drug discovery in various disease models. Genetic research indicates high conservation between zebrafish and human genomes, making it an ideal model for generating biologically relevant in vivo information on a range of test material. Due to their small size and the relatively simple nature of … The application of the zebrafish model in EDA-related research areas was verified by search in WoS for the zebrafish terms as keywords in topic/all databases, followed by classification per research area (Figure 1). Market Study Report, LLC, has added a research study on Military Shelter market which offers a concise summary regarding market valuation, market share, regional spectrum, revenue estimation and SWOT analysis of this business vertical. Or if the patient’s disease symptoms began during development in utero, knock-out or knock-in zebrafish embryos can be examined for gene expression changes (compared to embryos without the mutation) that could lead to abnormal development. Thus, any type of disease that causes changes in these body parts in humans could theoretically be modeled in zebrafish. Additionally, zebrafish are not useful models for human diseases that mainly take place in a tissue type or body part that zebrafish do not have (e.g., prostate, mammary glands, lungs). Due to the conservation of cell biological and developmental processes across all vertebrates, studies in fish can give great insight into human disease processes. According to the genome sequencing data, the zebrafish shares 70% genes with humans and more than 84% of genes that cause human genetic diseases are … Zebrafish embryos are able to absorb chemicals that have been added to their water, meaning it is easy to introduce changes to their genes using nothing more than chemical mutagens. Alternatively, these variants may occur in only a very small proportion of the population, since any deleterious genetic variant of major effect will have been selected against during evolution, or the variant may be recently occurring and thus not present in many individuals. But this approach does have its limitations. McCutcheon V (1) (2), Park E (2), Liu E (2), Wang Y (2), Wen XY (1) (2) (3) (4), Baker AJ (1) (2) (5) (6). Patients with Duchenne muscular dystrophy have been found to carry mutations in dystrophin and demonstrate childhood muscle weakness that gets progressively worse. Zebrafish Research and Biomedical Applications Zebrafish: From Basic Research to Drug Discovery. If one or more of the patient’s symptoms are observed in the zebrafish knock-out or knock-in model, the zebrafish can be used for further studies to help determine why the mutation in that gene causes the disease. Scientists use a variety of laboratory techniques to investigate the genetic cause of human diseases. For example, to date all proteins studied have a similar function in fish and mammals. Some of these reasons are outlined below: Zebrafish are vertebrates and therefore share a high degree of sequence and functional homology with mammals, including humans. The addition of the SETB1 mutation resulted in melanoma (indicated by the arrow). Their transparency also enables the visualization of fluorescently labeled tissues in transgenic zebrafish embryos. A trio of researchers, two with the University of Calgary, the other McMaster University, has found that vaping has the potential of impacting prenatal brain development in zebrafish. In the past two decades, Zebrafish has become one of the preferred in vivo model organisms for studying diverse processes like regeneration , embryogenesis [9, 10], autophagy , behaviour [12, 13] and sleep. Zebrafish, so named due to their stripes, prefer to live in large groups called shoals. Dr Caroline Brennan, from Queen Mary University of London, tells the NC3Rs the top five reasons why zebrafish are her model of choice. Although it is much more difficult to do, the exact mutation that the patient has can be introduced into zebrafish as well—this is called a “knock-in”. Zebrafish are tropical fresh-water fish in the minnow family. The lab has also initiated a study in collaboration … Therefore, animal mutagenesis studies can direct the human research. The team hopes to use the biological insights gained from zebrafish research to inform future studies. The timing of the adoption of zebrafish as an emerging model organism could not be better, as mouse studies often fail to translate to humans. As a result, they require much less space and are cheaper to maintain than mice. Such a catalog of phenotypes, combined with the experimental advantages of the zebrafish embryo, has a high potential to improve the drug screening process: in addition to information gained through in vitro interaction studies with isolated target molecules or through biochemical analyses of cultured cells, assays carried out in zebrafish embryos will provide primary readout information … New research on zebrafish could have interesting implications on humans and their use of cannabis. The one-cell-stage fertilized eggs can be easily injected with DNA or RNA to permanently modify their genetic makeup in order to generate transgenic or knock-out zebrafish lines. The zebrafish is an important and widely used vertebrate model organism in scientific research, for example in drug development, in particular pre-clinical development. Zebrafish larva, the stage of development from between three and thirty days post-fertilization, grow in length from approximately 3.5 to 8 millimeters. Mouse embryos develop inside the mother, and to access and manipulate them the mother would have to be sacrificed. However, there is a limit on what types of diseases can be studied in zebrafish. Less intrusive techniques minimise animal suffering. This is quite different from mice as they generally produce litters of one to 10 pups and can only bear approximately three litters in their lifetime. Add to this the wide range of environmental conditions that may impact on the disease occurrence, and the reluctance of individuals to be subjected to breeding schemes, and you can see why identification of disease causing alleles from human studies is problematic, despite vast amounts of sequence data. Also, mutations induced by mutagenesis do not have time to be selected against and thus give rise to stronger phenotypes that are far easier to map. This special series, published in Journal of Biomedical Science , focuses on the use of zebrafish for discovering novel development and pathogenesis pathways, and developing new therapies against diseases. Easier to house and care for than rodents. Source: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3484855/. Human diseases caused by genes that do not exist in zebrafish require a different animal model. In fact, 70% of human genes are found in zebrafish. In particular, we outline recent genetic and technological developments allowing for in vivo examinations, high-throughput screening and whole-brain analyses in larval and adult zebrafish. The ability of zebrafish to generate many embryos every time they breed makes them especially useful for high throughput drug screening. Source: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3348545/. Research often utilizes patients’ cells or tissue samples, but to determine if a mutation in a specific gene can cause a patient’s symptoms, we often need experimental animal models. Zebrafish is a small fresh water fish that has been used for decades as a classical developmental biology research model (Streisinger et al., 1981; Kimmel, 1989). Here, we investigated the developmental toxicity of few-layered BP toward the zebrafish. 3.Impact of any genetic mutation or drug treatment is easy to see. tallafuss@uoneuro.uoregon.edu The generation of a knock-out of the dystrophin gene in zebrafish has been shown to closely resemble the severity and progression of the human disease Duchenne muscular dystrophy. Ensuring a ready supply of animals for research is also easier with zebrafish. Furthermore, considering the emerging use of zebrafish in the novel worldwide research endeavours, we aimed to compare and elaborate the zebrafish neurophysiology model in PD research with regard to disease development factors, cause-effect relationship of OS and comorbidities (focussing on sleep disturbances), and the pharmacological potential of antioxidant molecules. Mouse embryos are not clear and develop inside the mother, so the observation of live embryo development like that in zebrafish is not possible. The University of Mississippi has also had success with Zebrafish studies, using the fish to identify mistletoe and its inherent compounds as a potential treatment for epilepsy. The release of BP into aquatic ecosystems and the potential toxic effects on aquatic organisms are becoming major concerns. Does this surprise you? Although humans may appear to be extremely different than zebrafish, we are actually much more similar to them than you might think. Cardiovascular disease (CVD) is the leading cause of global mortality, which has caused a huge burden on the quality of human life. In the wild, they are found in rivers and ponds of India, however they are now often available in pet shops. Black phosphorus (BP) has extensive applications in various fields. Zebrafish embryos and larvae are completely transparent, meaning that it is possible to follow the impact of a genetic manipulation or pharmacological treatment using non-invasive imaging techniques. Easier to house and care for than rodents. Moreover, zebrafish have two eyes, a mouth, brain, spinal cord, intestine, pancreas, liver, bile ducts, kidney, esophagus, heart, ear, nose, muscle, blood, bone, cartilage, and teeth. Although sometimes limited by the short efficacy period and confounding off-target effects (reviewed in Bedell et al., 2011), the use of morpholinos in zebrafish research, beginning at the turn of this century, tremendously accelerated zebrafish loss-of-function studies and solidified the relevance of investigating zebrafish orthologs of human disease genes. Random mutations are introduced into the genome and the offspring are screened for the phenotype of interest. His research was long based on the larvae of fruitfly, but the lab recently started using zebrafish larvae. These results helped to establish that SETDB1 is an important gene in melanoma growth. Presidential Early Career Award for Scientists and Engineers (PECASE), National Medal of Technology & Innovation, Samuel J. Heyman Service to America Medals, Advancing Computational and Structural Biology, Uncovering New Opportunities for Natural Products, Unlocking the Potential of RNA Biology and Therapeutics, Assistant Clinical Investigator in Neurogenetics, Tenure-Track/Tenure-Eligible Investigator, NCI-DCEG, Nurturing the Next Generation of Clinical Researchers, 70% of human genes are found in zebrafish, http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3484855/, http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3348545/, Little Fish in a Big Pond Reveal New Answers to Old Questions, Innovation Awards Spark New Intramural Collaborations, A Multi-Front Effort to Combat Coronavirus, IRP’s Luigi Notarangelo Elected to National Academy of Medicine, IRP’s Michael Lenardo Elected to National Academy of Sciences. Although the main focus of zebrafish research has traditionally been on developmental biology, keeping and observing zebrafish in the lab led to the identification of diseases similar to humans, such as cancer, which subsequently became a subject for study. (2018) using zebrafish larvae to test the involvement of membrane remodeling in hepatotoxicity showed that co-exposure of obese zebrafish larvae to benzo[a]pyrene and ethanol induced in vivo hepatotoxicity through membrane remodeling. A Model of Excitotoxic Brain Injury in Larval Zebrafish: Potential Application for High-Throughput Drug Evaluation to Treat Traumatic Brain Injury. The tropical zebrafish is a popular aquarium fish, yet it is also an important vertebrate model organism in scientific research for studying developmental processes and human diseases. Tuesday, August 9, 2016. Other areas of study include Alzheimer’s , the endocannabinoid system, and opioid systems, especially in addiction and substance abuse. As the animals are reared in a controlled environment, variation due to environment is minimised. The search for robust fear inducing stimuli in zebrafish research Zebrafish behavioral research has grown by leaps and bounds, and behavioral paradigms are being developed with the aim of better understanding mechanisms that might underlie aberrant behavioral phenotypes. This FOA encourages investigator-initiated NIH Research Project Grant (R01) applications designed to exploit the power of the zebrafish as a vertebrate model for biomedical and behavioral research. Zebrafish offspring also grow and develop very quickly. Not only does this add to the refinement of animal usage, it also minimises the number of animals that need to be used because it reduces the between subject variation that can be caused by stress. Here in the NIH Undiagnosed Diseases Program, we perform studies using zebrafish as one of several approaches to investigate the potential involvement of altered genes in our patients’ extremely rare diseases. In both humans and the zebrafish model, the loss of dystrophin gradually leads to necrotic muscle fibers that are replaced by inflammatory cells, fibrosis, and abnormally sized muscle fibers. Often a patient’s DNA is sequenced in order to find a mutation in a gene that could potentially cause his or her disease symptoms. As the name suggests, human genome wide association studies (GWAS), can only show a statistical association between a particular genetic variant and a given disease. Working with mice in this way is much more complicated. Zebrafish are able to withstand much higher levels of chemical mutagens than can be tolerated by rodents so it is possible to induce a much higher density of mutations in their genome. The invasive procedures avoided not only impact on welfare, but may also affect the experimental outcome, so the transparent nature of zebrafish larvae could also mean results are more accurate and easier to reproduce. Many of the genes and critical pathways that are required to grow these features are highly conserved between humans and zebrafish. Despite the growing interest in ‘big data’ approaches to studying the genetics of human disease, currently there is still a need to work in animal model systems. Although possible in rodents, forward genetic screening is far easier in zebrafish and, as highlighted above, there is a strong scientific and moral case for the zebrafish model. While mice and rats have been common choices for modeling human diseases in the past, the … Recent research from Imran et al. Gibbs Building, 215 Euston Road, London, NW1 2BE | Tel: 020 7611 2233 | Fax: 020 7611 2260 | enquiries@nc3rs.org.uk, Five reasons why zebrafish make excellent research models. For instance, zebrafish with the mutated MYO18B gene can serve as a model for human myopathy. The most commonly identified mutation in human melanomas—a single amino acid change in the gene BRAF—was created in zebrafish to make a knock-in model. It is also notable for its regenerative abilities, and has been modified by researchers to produce many transgenic strains. 2. When another commonly observed melanoma mutation of the gene SETDB1 was added to the BRAF knock-in zebrafish, a melanoma rapidly developed. In addition to utilizing zebrafish disease models to characterize human diseases, researchers can also identify and test new drugs to treat the diseases being modeled. Zebrafish (Danio rerio) is a fresh water fish that inhabits rivers in India, Pakistan and other places in Asia. Many structural, functional and developmental similarities exist between zebrafish and human retinas, providing researchers with an excellent model to study human vision. In the present study, a rapid zebrafish behavioral profiling assay was developed to characterize the neurodevelopmental effects of environmental substances by quantitatively evaluating multiple spontaneous movement features of zebrafish embryos. Forward genetic mutagenesis studies in animal models can avoid these issues. For the majority of human diseases, genetic variations that associate with disease are of very minor effect, meaning that vast amounts of sequencing data are required before one can assign statistical significance to an association, which is hugely time consuming and expensive. The Zebrafish (Danio Rerio) is a Teleost fish, which offers several practical advantages concerning manipulation, maintenance and versatility as well as short life cycle, low cost and physiological similarity with most farmed species.Zebrafish have been used as model for several aquaculture‐relevant infectious agents, since the cost of infections to aquaculture can be great, … Tallafuss A(1), Gibson D, Morcos P, Li Y, Seredick S, Eisen J, Washbourne P. Author information: (1)Institute of Neuroscience, University of Oregon, Eugene, OR 97403, USA. Scientific experiments are generally repeated multiple times in order to prove that the results are accurate, so having an animal that can produce a large number of offspring over and over is helpful. To keep the embryos alive after fertilizing or injecting them, they would need to be transplanted into another female mouse, as well. This result led scientists to develop a therapy for nonalcoholic fatty liver disease and associated risk factors. Human melanoma has also been successfully modeled in zebrafish. While mice are evolutionarily more similar to humans because they are mammals, zebrafish have several advantages over their furry competitors. For instance, the structure of the muscle fibers can be examined for abnormalities under the microscope if the patient has a muscle disease. This minimises housing stress and the impact such stress may have on the outcome of experiments. Another advantage is that adult zebrafish breed readily (approximately every 10 days) and can produce as many as 50 to 300 eggs at a time. The name “zebrafish” comes from the horizontal blue stripes on each side of their bodies. Zebrafish embryos are also laid and fertilized externally, which allows them to be easily manipulated in a variety of ways. While mice and rats have been common choices for modeling human diseases in the past, the use of zebrafish is rapidly gaining popularity. Turning gene function ON and OFF using sense and antisense photo-morpholinos in zebrafish. Zebrafish potential for EDA application Zebrafish in EDA-relevant research areas. Furthermore, zebrafish embryos are clear, which allows scientists to watch the fertilized eggs grow into fully formed baby fish under a microscope. Building on earlier work characterizing zebrafish ventricular myocyte ion currents (Brette et al., 2008), Nemtsas et al. Scientists use a variety of laboratory techniques to investigate the genetic cause of human diseases. One important advantage of zebrafish is that the adults are small and prefer to be housed in large groups, or “shoals”. Images of a knock-in zebrafish that expresses the BRAF mutation alone (top) and one that was also injected with a transposon-based vector (miniCoopR) containing a mutant form of the gene SETDB1 (bottom). We provide customized testing models and methods for a range of substances including extracts, complex mixtures and purified compounds. The zebrafish research has gained further momentum in recent years due to two major technological breakthroughs: (1) completion of its genome sequencing (Howe et al., 2013) and (2) development of genome-editing technology (Gaj et al., 2013). We also summarize the application of these molecular techniques to the understanding of neuropsychiatric disease, outlining the potential of zebrafish for modeling complex brain disorders, including attention-deficit/hyperactivity … Research often utilizes patients’ cells or tissue samples, but to determine if a mutation in a specific gene can cause a patient’s symptoms, we often need experimental animal models. Assuming that the exact mutation does not occur in humans, it is still likely that any variant in a gene that shows a strong phenotype in animal studies will contribute to the disease phenotype in humans. The small size and rapid development of the zebrafish make it a useful vertebrate model for assessing the potential effects of substances on growth and development using high-throughput screening methods (as reviewed in Planchart et al. This FOA encourages investigator-initiated applications designed to exploit the power of the zebrafish as a vertebrate model for biomedical and behavioral research. Since cancers are caused by a combination of several genetic alterations, this knock-in zebrafish line was used to screen other potential cancer causing mutations. Let me explain. In recent decades, zebrafish has entered the field of CVD as an important model organism. To learn more about how zebrafish contribute to biomedical science and human health, visit the websites for the Trans-NIH Zebrafish Initiative website and the NICHD Zebrafish Core. Zebrafish have a much larger number of offspring in each generation than rodents. Get monthly updates in your inbox from the NC3Rs on funding opportunities, events and publications. For many, zebrafish are becoming an increasingly popular choice of model. Rodents have 5-10 offspring per pairing, in comparison to the 200-300 obtained from fish. How do the benefits of using a zebrafish model apply to genetic research? While mice have been the predominant animal bridge between the bench and bedside in the past, recent studies have demonstrated the potential of zebrafish to serve as a tractable alternative to mice. Recently, Zebrafish has sparked interest in other branches of the biomedical research … Zebrafish produce hundreds of offspring at weekly intervals providing scientists with an ample … The NIH Zebrafish Core houses hundreds of thousands of zebrafish in a state-of-the-art facility. Due to their small size and the relatively simple nature of their natural environment, it is easier to keep zebrafish in what appear to be more natural conditions than it is possible to simulate for mammals. To determine if loss of function of that gene could cause the symptoms seen in the patient, the same gene is mutated or “knocked-out” in zebrafish, and then the fish are examined for similar symptoms. Therefore, experimental animal models of CVD have become essential tools for analyzing the pathogenesis, developing drug screening, and testing potential therapeutic strategies. Those examples of how humans and zebrafish can manifest the same disease despite how different we appear make it is easy to understand why zebrafish are becoming a well-accepted animal model. When using animals in research, it is important to minimise animal suffering by using the least sentient organism possible to answer the question at hand. For a patient with a neurological disease, the neurons of knock-out embryos can be fluorescently labeled to see if they form incorrectly. In length from approximately 3.5 to 8 millimeters in dystrophin and demonstrate childhood muscle weakness that progressively. Is rapidly gaining popularity, any type of disease that causes changes in these body parts in could. Blue stripes on each side of their bodies toxic effects on aquatic organisms are becoming major concerns zebrafish.! Serve as a model of Excitotoxic Brain Injury develop inside the mother, and opioid systems, in... 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