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Concept zebrafish russell

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Concept zebrafish russell

  1. 1. Zebrafish Models of Batten Disease Kim Wager, Courtesy of the Laboratory of Claire Russell, PhD, The Royal Veterinary College, London, U.K. crussell@rvc.ac.uk Why do we need animal models of Batten’s disease? •To improve our understanding of the disease e.g. Which brain cells are affected and why? What molecules are involved in the disease? •To develop and test new treatments e.g. To check that new drugs are safe and what dose works best. Why do we need Zebrafish models of Batten’s disease? • Zebrafish can speed up drug discovery. What makes Zebrafish a good model for Batten’s disease? •Zebrafish are transparent. This means we can look inside their brains while they are alive. •The Zebrafish brain is surprisingly similar to human •Their brain’s contain all the same types of cell as human brains. •The chemicals used by zebrafish brain cells are the same as in humans. •Zebrafish develop external to the mother and very fast. This means signs and symptoms progress very quickly. •Zebrafish possess all the known Batten’s disease genes and so can model all types. X The Zebrafish eye is a great tool to study retinal degeneration How are drugs tested on Zebrafish? • Embryonic fish are laid out on a grid to which candidate drugs can be added. • Further experiments can then be carried out on the fish to test if the drugs have had any effect. • Do characteristics of the disease improve? • Do the fish have an increased life span? • Do any symptoms the fish have get better? How do we test for Batten’s disease in Zebrafish? •Do lysosomes become enlarged? •What storage material is present in the lysosomes? •Are neurons dying; if so why? •Do support cells (astrocytes) become activated? •Do neurons get too excitable? •Do the zebrafish suffer epileptic seizures? •Is the blood brain barrier intact? •Is there any inflammation in the brain? •Are structures inside cells (e.g. mitochondria) working properly? Potential new drugs are developed First these may be tried on cell cultures Zebrafish can be used before mice, they are cheaper and quicker Promisingresults can then move on to mouse studies If the drug is safe and seems to work, human trials are started Safe, effective drugs are brought to market Breed fish Embryos are collected and laid out on a grid so that we know which fish have be given specific drugs and which dose Embryonic fish We can observe the storage of unwanted molecules in the brain Brain cells and all their interactions can be observed in living Zebrafish Credit: Dominik Paquet Credit: Hideo Otsuna Credit: Kara Cerveny