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Zebra fish model
The document discusses the use of zebrafish as a model organism to screen pharmaceutical compounds. Some key points: - Zebrafish are commonly used as they are small, breed readily, and develop quickly, allowing for large studies. Their embryos are transparent, allowing effects to be easily observed. - Zebrafish have been used as a model since the 1970s and their genome has been fully sequenced, showing similarities to humans. They can be used to study cancer, Alzheimer's, depression, and toxicity. - Advantages include low cost, high fecundity, and optical clarity which allows internal structures to be viewed easily. However, they may lack some clinical relevance due to differences from humans.
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Zebra fish model
- 1. Zebra Fish modelto screen Pharmaceutical compounds Presented by: Aditya Singh PC/2019/212 Pharmacology & Toxicology Subject code: PC-611 Subject teacher: Dr. Dharmendra Kumar Khatri
- 2. General Introduction • Itis a tropical fresh water fish • It is abundant in the Ganges and Brahmaputra river • Biological name: Danio rerio • Size is usually small i.e- 1-1.5 inches hence easy to breed and captivate 1-1.5 inch
- 3. History of itsusage 1972 • At the University of Oregon, USA • Dr. Scitsinger First to develop zebrafish as an animal model to screen drugs 1975 • Zebrafish was sent into space 1987 • First transgenic variant of zebrafish model developed 1990- 95 • First cortisol assay done • Mutagenesis done • Cancer studies • Anxiety, learning, sleep and cognitive experiments performed 2005 • EEG of brain • c-fos assays performed 2013 • Sanger institute sequenced full genome and created a gene library Tavares B, Santos Lopes S. The importance of Zebrafish in biomedical research. Acta Med Port. 2013 Sep-Oct;26(5):583-92.
- 4. Life cycle ofZebrafish Ribas, Laia, and Francesc Piferrer. "The zebrafish (D anio rerio) as a model organism, with emphasis on applications for finfish aquaculture research." Reviews in Aquaculture 6.4 (2014): 209-240. Zygote Blastula Gastrula Hatching Larvae Juvenile Adult
- 5. Zebrafish: Eureka! • Zebrafish is named after its five blue striped horizontal sections on its body • These stripes resembles the stripes of zebra and extend up to the caudal fin • It is laterally compressed with mouth directed upwards Anatomy of zebrafish larva Anatomy of a male adult zebrafish Engeszer, Raymond E., et al. "Zebrafish in the wild: a review of natural history and new notes from the field." Zebrafish 4.1 (2007): 21-40.
- 6. Advantages of themodel When using animals in research, it is important to minimise animal, scientific reasons why ‘lower’ organisms, such as zebrafish, can create a better model system. • Small size and speedy growth: Adult zebrafish are small in size, they grow quickly, and they breed readily. They can reach sexual maturity in three months in the lab, and each adult female can produce hundreds of eggs a week. Conducting larger studies with higher numbers in your exposure groups is much easier with zebrafish than with mice. • Easier to house and care than rodents Due to their small size and the relatively simple nature of their natural environment, it is easier to keep zebrafish in more natural conditions than it is possible to simulate for mammals. minimises housing stress, it also minimises the number of animals that need to be used because it reduces the subject variation that can be caused by stress. • External fertilization and development: The eggs are fertilized and undergo development outside the mother’s body, rather than the internal development of mammals or even the internal fertilization of birds, amphibians and reptiles. This allows researchers to examine and manipulate the embryos from the moment they are fertilized • Lots of offspring Zebrafish have a much larger number of offspring in each generation than rodents. Rodents have 5-10 offspring per pairing, in comparison to the 200-300 obtained from fish. Zebrafish offspring also grow and develop very quickly. Zebrafish storage tanks Siccardi III, Anthony J., et al. "Growth and survival of zebrafish (Danio rerio) fed different commercial and laboratory diets." Zebrafish 6.3 (2009): 275-280.
- 7. Advantages of themodel • Impact of any genetic mutation or drug treatment is easy to see 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 introduce genetic changes 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. • See-through embryos: The optical clarity of zebrafish embryos and the chorions that surround them offers an amazing view of morphological development, organ development and function. • Homology to humans: Zebrafish have many of the same genes, tissues, and organ systems as humans. Because zebrafish are more similar to humans than invertebrate models (such as the worm Caenorhabditis elegans and the fly Drosophila melanogaster), discoveries made in zebrafish are more likely to be directly applicable to humans than those made in invertebrate systems. Howe, K., Clark, M., Torroja, C. et al. The zebrafish reference genome sequence and its relationship to the human genome. Nature 496, 498–503 (2013).
- 8. Zebrafish model incancer Mutagenesis or transplant Dexamethasone Immunosuppression Chemical treatment Tumour cells injected Tumour cells excised from humans Mutagenesis Transgenesis Transplant Treatment and further studies Adult fish Embryo stage Astone, M., Dankert, E.N., Alam, S.K. et al. Fishing for cures: The alLURE of using zebrafish to develop precision oncology therapies. npj Precision Onc 1, 39 (2017).
- 9. Zebrafish model inAlzheimer's Acoustic stimuli Startle response Aβ1-42 amyloid plagues and tau tangles study can be performed Trimethlytin chloride (TMT) neurobehavioral toxicity, specifically, apoptosis in the tail, modulations in photomotor response and frequency of tail flexion Okadaic acid Deficits in cognition , learning and locomotor activity Saleem, S., Kannan, R.R. Zebrafish: an emerging real-time model system to study Alzheimer’s disease and neurospecific drug discovery. Cell Death Discov. 4, 45 (2018). Hind brain ventricle or intraventricular
- 10. Zebrafish model inDepression studies
- 11. Zebrafish model fortoxicity studies 1. Ecotoxicology: OECD TG- 236 : Fish embryo toxicity for LC-50 2. Monitoring endocrine disruptors 3. Teratogenicity 4. Neurobehavioral toxicity 5. Cardiotoxicity 6. Ototoxicity Toxicity endpoints Kathryn Bambino, Jaime Chu, Chapter Nine - Zebrafish in Toxicology and Environmental Health, Current Topics in Developmental Biology, Academic Press, Volume 124,2017, Pages 331-367.
- 12. Disadvantages of themodel 1. Zebrafish as a model lacks some clinical applicability 2. Zebrafishes are extensively used to study developmental biology but lacks direct co-relation to humans as they can regenerate their organs 3. Mostly chemical treatment and inducers are added in water, but the quantity entering actually into the bodies are highly variable 4. Zebrafish model has been used extensively for neurological studies, but neurons in them divide abruptly which is very impractical to co- relate to humans
- 13. References 1. Tavares B,Santos Lopes S. The importance of Zebrafish in biomedical research. Acta Med Port. 2013 Sep- Oct;26(5):583-92. 2. Ribas, Laia, and Francesc Piferrer. "The zebrafish (D anio rerio) as a model organism, with emphasis on applications for finfish aquaculture research." Reviews in Aquaculture 6.4 (2014): 209-240. 3. Engeszer, Raymond E., et al. "Zebrafish in the wild: a review of natural history and new notes from the field." Zebrafish 4.1 (2007): 21-40. 4. Siccardi III, Anthony J., et al. "Growth and survival of zebrafish (Danio rerio) fed different commercial and laboratory diets." Zebrafish 6.3 (2009): 275-280. 5. Howe, K., Clark, M., Torroja, C. et al. The zebrafish reference genome sequence and its relationship to the human genome. Nature 496, 498–503 (2013). 6. Astone, M., Dankert, E.N., Alam, S.K. et al. Fishing for cures: The alLURE of using zebrafish to develop precision oncology therapies. npj Precision Onc 1, 39 (2017). 7. Saleem, S., Kannan, R.R. Zebrafish: an emerging real-time model system to study Alzheimer’s disease and neurospecific drug discovery. Cell Death Discov. 4, 45 (2018). 8. Kathryn Bambino, Jaime Chu, Chapter Nine - Zebrafish in Toxicology and Environmental Health, Current Topics in Developmental Biology, Academic Press,Volume 124,2017, Pages 331-367.