Zebrafish--an Emerging Genetic Model for the Study of Cytokines and Hematopoiesis in the Era of Functional Genomics

Now that whole genomes are sequenced, the identification of gene function rather than gene discovery is a major challenge. Saturation mutagenesis and screening for mutant phenotypes are methods that allow sampling of the genome for lesions in genes critical for particular physiological processes. This approach promises to provide new insights into gene function, even for molecularly well-characterized processes such as hematopoiesis and cytokine signaling. Animal models for such genetic approaches have traditionally included Drosophila and the mouse. Recently, the zebrafish (Danio rerio) has emerged as a flexible and informative vertebrate for genetic studies. Zebrafish hematopoiesis has a morphological and molecular complexity closer to that of mammals than does Drosophila, providing scope for recognizing mutant zebrafish phenotypes representing finely tuned lesions in these processes. Compared to mice, zebrafish represent an economical, flexible, and genetically tractable animal model for mutagenesis studies. The structure of the teleost genome creates several phylogenetic issues in assessing zebrafish and piscine orthologues and paralogues of known mammalian genes, here exemplified by a cytokine ligand (interleukin-1beta), kinase receptors (c-kit and c-fins), and a family of intracellular signaling molecules (JAK kinases). Several anemic zebrafish mutants are now genetically characterized, and others present hematopoietic phenotypes that promise novel insights into the regulation of hematopoiesis.