Shafizadeh, E., and Paw, B.H. (2004) Zebrafish as a model of human hematologic disorders. Current opinion in hematology. 11(4):255-261.
PURPOSE OF REVIEW: This review summarizes the status of zebrafish as a genetic model to study human hematological disorders. Much of our current understanding of the function of genes modulating the process of hematopoietic stem cell generation, specification, and differentiation has come from mutant analysis. Because of the transparency of zebrafish embryos that allows for direct visualization of circulating erythroid cells, mutations affecting zebrafish erythropoiesis were among the first characterized mutants through positional cloning and candidate gene strategies. RECENT FINDINGS: New technologies have evolved that allow for generation, detection, and characterization of lineage specific alterations in the hematopoietic system. We will also briefly discuss the applications of several of these technologies such as targeted gene knockdown using antisense morpholinos, small molecule screen, transgenesis, and cell transplantation as related to blood disorders and hematopoietic development. SUMMARY: The combination of phenotype-driven forward genetic analyses and innovative technical advances has conferred zebrafish as a powerful genetic model to further dissect the function of hematopoietic genes. Through the use of available resources, the identification of novel genes or novel function for known hematopoietic genes will have important implications for our understanding of human disease pathogenesis, treatment, and prevention.