Frontiers in Genetics (Aug 2018)
Rare Genetic Blood Disease Modeling in Zebrafish
Abstract
Hematopoiesis results in the correct formation of all the different blood cell types. In mammals, it starts from specific hematopoietic stem and precursor cells residing in the bone marrow. Mature blood cells are responsible for supplying oxygen to every cell of the organism and for the protection against pathogens. Therefore, inherited or de novo genetic mutations affecting blood cell formation or the regulation of their activity are responsible for numerous diseases including anemia, immunodeficiency, autoimmunity, hyper- or hypo-inflammation, and cancer. By definition, an animal disease model is an analogous version of a specific clinical condition developed by researchers to gain information about its pathophysiology. Among all the model species used in comparative medicine, mice continue to be the most common and accepted model for biomedical research. However, because of the complexity of human diseases and the intrinsic differences between humans and other species, the use of several models (possibly in distinct species) can often be more helpful and informative than the use of a single model. In recent decades, the zebrafish (Danio rerio) has become increasingly popular among researchers, because it represents an inexpensive alternative compared to mammalian models, such as mice. Numerous advantages make it an excellent animal model to be used in genetic studies and in particular in modeling human blood diseases. Comparing zebrafish hematopoiesis to mammals, it is highly conserved with few, significant differences. In addition, the zebrafish model has a high-quality, complete genomic sequence available that shows a high level of evolutionary conservation with the human genome, empowering genetic and genomic approaches. Moreover, the external fertilization, the high fecundity and the transparency of their embryos facilitate rapid, in vivo analysis of phenotypes. In addition, the ability to manipulate its genome using the last genome editing technologies, provides powerful tools for developing new disease models and understanding the pathophysiology of human disorders. This review provides an overview of the different approaches and techniques that can be used to model genetic diseases in zebrafish, discussing how this animal model has contributed to the understanding of genetic diseases, with a specific focus on the blood disorders.
Keywords
