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potential application of zebrafish in research

2. 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. The name “zebrafish” comes from the horizontal blue stripes on each side of their bodies. Random mutations are introduced into the genome and the offspring are screened for the phenotype of interest. To keep the embryos alive after fertilizing or injecting them, they would need to be transplanted into another female mouse, as well. 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 zebrafish is an important and widely used vertebrate model organism in scientific research, for example in drug development, in particular pre-clinical development. 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. Source: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3484855/. These results helped to establish that SETDB1 is an important gene in melanoma growth. 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. 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. 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. Less intrusive techniques minimise animal suffering. The lab has also initiated a study in collaboration … A Model of Excitotoxic Brain Injury in Larval Zebrafish: Potential Application for High-Throughput Drug Evaluation to Treat Traumatic Brain Injury. Black phosphorus (BP) has extensive applications in various fields. Zebrafish (Danio rerio) is a fresh water fish that inhabits rivers in India, Pakistan and other places in Asia. 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). 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”. 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. Ensuring a ready supply of animals for research is also easier with zebrafish. 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. Zebrafish, so named due to their stripes, prefer to live in large groups called shoals. It is also notable for its regenerative abilities, and has been modified by researchers to produce many transgenic strains. 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. As a result, they require much less space and are cheaper to maintain than mice. How do the benefits of using a zebrafish model apply to genetic research? 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. 3.Impact of any genetic mutation or drug treatment is easy to see. 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. 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. Human diseases caused by genes that do not exist in zebrafish require a different animal model. Scientists use a variety of laboratory techniques to investigate the genetic cause of human diseases. For a patient with a neurological disease, the neurons of knock-out embryos can be fluorescently labeled to see if they form incorrectly. For instance, zebrafish with the mutated MYO18B gene can serve as a model for human myopathy. Mouse embryos are not clear and develop inside the mother, so the observation of live embryo development like that in zebrafish is not possible. 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. For many, zebrafish are becoming an increasingly popular choice of model. Tuesday, August 9, 2016. Turning gene function ON and OFF using sense and antisense photo-morpholinos in zebrafish. 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. 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. 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. New research on zebrafish could have interesting implications on humans and their use of cannabis. In vitro fertilization can be performed if necessary. His research was long based on the larvae of fruitfly, but the lab recently started using zebrafish larvae. Zebrafish have a much larger number of offspring in each generation than rodents. 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. Building on earlier work characterizing zebrafish ventricular myocyte ion currents (Brette et al., 2008), Nemtsas et al. 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. 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. 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. 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. 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. 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. Many structural, functional and developmental similarities exist between zebrafish and human retinas, providing researchers with an excellent model to study human vision. Zebrafish larva, the stage of development from between three and thirty days post-fertilization, grow in length from approximately 3.5 to 8 millimeters. 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. 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. Patients with Duchenne muscular dystrophy have been found to carry mutations in dystrophin and demonstrate childhood muscle weakness that gets progressively worse. 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. 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. 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. Other areas of study include Alzheimer’s , the endocannabinoid system, and opioid systems, especially in addiction and substance abuse. This figure shows visual differences in muscle between wild-type zebrafish larva (A, B, C) and distrophic larva (A’, B’, C’). 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. Although humans may appear to be extremely different than zebrafish, we are actually much more similar to them than you might think. The team hopes to use the biological insights gained from zebrafish research to inform future studies. tallafuss@uoneuro.uoregon.edu The release of BP into aquatic ecosystems and the potential toxic effects on aquatic organisms are becoming major concerns. 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. 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. 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). Due to their small size and the relatively simple nature of … 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. Let me explain. Scientists use a variety of laboratory techniques to investigate the genetic cause of human diseases. 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 embryos are also laid and fertilized externally, which allows them to be easily manipulated in a variety of ways. The NIH Zebrafish Core houses hundreds of thousands of zebrafish in a state-of-the-art facility. Thus, any type of disease that causes changes in these body parts in humans could theoretically be modeled in zebrafish. 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. This FOA encourages investigator-initiated applications designed to exploit the power of the zebrafish as a vertebrate model for biomedical and behavioral research. 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). In the wild, they are found in rivers and ponds of India, however they are now often available in pet shops. Therefore, animal mutagenesis studies can direct the human research. 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. Rodents have 5-10 offspring per pairing, in comparison to the 200-300 obtained from fish. Therefore, experimental animal models of CVD have become essential tools for analyzing the pathogenesis, developing drug screening, and testing potential therapeutic strategies. Zebrafish potential for EDA application Zebrafish in EDA-relevant research areas. In fact, 70% of human genes are found in zebrafish. But, there are also purely scientific reasons why ‘lower’ organisms, such as zebrafish, can create a better model system. Source: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3348545/. 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. 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 … Zebrafish are tropical fresh-water fish in the minnow family. Recently, Zebrafish has sparked interest in other branches of the biomedical research because of its emerging potential for drug discovery in various disease models. While mice are evolutionarily more similar to humans because they are mammals, zebrafish have several advantages over their furry competitors. 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. For instance, the structure of the muscle fibers can be examined for abnormalities under the microscope if the patient has a muscle disease. Their transparency also enables the visualization of fluorescently labeled tissues in transgenic zebrafish embryos. The addition of the SETB1 mutation resulted in melanoma (indicated by the arrow). The ability of zebrafish to generate many embryos every time they breed makes them especially useful for high throughput drug screening. But this approach does have its limitations. 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. Does this surprise you? (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. Dr Caroline Brennan, from Queen Mary University of London, tells the NC3Rs the top five reasons why zebrafish are her model of choice. Cardiovascular disease (CVD) is the leading cause of global mortality, which has caused a huge burden on the quality of human life. 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. Recent research from Imran et al. Working with mice in this way is much more complicated. 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. 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). 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