They have also shown to be successful in isolating candidate genes responsible for human diseases.
Zebrafish screens are feasible and were first used to identify genes involved in vertebrate development. Forward genetic approaches involve random mutagenesis in the embryo to alter gene function and assessing phenotypes as a starting point to find the causative gene. Here, we will review kidney-related research in zebrafish and discuss the advantages and potential caveats involved of using this organism as a model.įorward and reverse genetic approaches can easily be used in the zebrafish to enable the study of genes. A significant amount of research has been carried out to study renal function and disease using zebrafish. Zebrafish have also been useful in the field of cardiology specifically in the study of heart regeneration mechanisms and can show cardiac failure when the same genes known to cause dilated cardiomyopathy in humans are knocked down in the zebrafish. Zebrafish adults from the c-myb hyper mutant line developed acute myeloid leukaemia-like or acute lymphoid leukaemia-like disorders due to the hyperactivity of the transcription factor c-myb (Myb proto-oncogene protein)-such abnormalities in man lead to many haematopoietic disorders. For example, via the use of chemicals, tumours can be induced in a number of organs proving to be useful models of cancer.
Zebrafish have long been used in other fields of research to gain a better insight into various disease states. Furthermore, genetic editing techniques such as transcription activator-like effector nucleases (TALENs), zinc finger nucleases and more recently, the Clustered regularly interspaced short palindromic repeat (CRISPR)- Cas9 system can be easily employed in the zebrafish to study gene function and the consequences of its absence/modification. With regards to homology between the two species, there is high conservation of functional domains between human and zebrafish proteins, where at least 70% of zebrafish proteins have a human orthologue and 47% of human genes have a one-to-one association with orthologue in zebrafish. They are especially useful for the study of genetic diseases, as they are very amenable to genetic manipulations, such as through microinjections of DNA and RNA even at the one-cell stage of life. These embryos can be analysed for a phenotype of interest rapidly due to their transparent nature, and pigment can be reduced by chemical treatments and albino strains enabling phenotypic analysis at later stages. This allows testing of various compounds and even drug screening is feasible and potentially high throughput. Zebrafish has advantages over mammalian models such as mice ( Mus musculus) in that pairings can produce a large number (~ 50–200) of offspring that can grow to adulthood within 3 months. Zebrafish sperm can also be cryopreserved, reducing the need for live culture and therefore decreasing resource use. Zebrafish embryos at the earlier stages of development (before 5.0 days post-fertilisation) are considered to experience little to no pain and therefore are not protected under the animal experimentation regulations, thus making them a useful replacement model for mammalian models, such as mice and rats. But advances in technology have facilitated the growth of zebrafish as models to study organ-specific diseases, such as kidney disorders. Zebrafish ( Danio rerio) have been established as a model for development and reproduction studies since the 1930s. Animal studies are a major tool in research, providing better understanding of normal physiology and mechanisms of disease and to test potential therapies. Factors such as rising obesity, diabetes and hypertension have been shown to play a role in the manifestation of kidney dysfunction, but more research is needed to understand the pathophysiology behind the disease. Kidney disease is a global problem with around three million people diagnosed in the UK alone and up to a million people undiagnosed.
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