Content area
Full text
Zebrafish have been widely used as a model system for studying developmental processes, but in the last decade, they have also emerged as a valuable system for modeling human disease. The development and function of zebrafish organs are strikingly similar to those of humans, and the ease of creating mutant or transgenic fish has facilitated the generation of disease models. Here, we highlight the use of zebrafish for defining disease pathways and for discovering new therapies.
Introduction
Danio reno, better known as zebrafish, is a small vertebrate tropical water fish that has become one of the favored animal model systems for studying developmental processes and human disorders (Figure 1). Zebrafish share a high genetic similarity to humans, and approximately 70% of all human disease genes have functional homologs in zebrafish (1). Many advantages of zebrafish biology make it an attractive model for researchers: they have a high fecundity and can lay 200-300 eggs/week, the embryos are transparent and develop outside the body, making them particularly easy to study, and development is rapid, with major organs formed by 24 hours after fertilization. In addition, zebrafish are easy and inexpensive to raise and maintain, making it possible to keep rñousands of animals in a laboratory at a reasonable cost. As a nonmammalian species, zebrafish do have certain disadvantages for modeling human disease; they lack some of the mammalian organs, such as lung and mammary gland, and phenotypic characteristics of diseases caused by orthologos genes can be very different in fish and human. In addition, the zebrafish genome includes many gene duplications, resulting in gene subfunctionalization and neofunctionalization (2).
Took to model disease in zebrafish. Traditionally, zebrafish have been utilized as a forward genetic system. Chemical and insertional mutagenesis screens have led to the identification of a myriad of mutants with disruption of conserved genes that correlate to human disease loci (refs. 3, 4, and Figure 2). In addition, the DNA transposon system SleepingBeauty - used in mouse for insertional somatic mutagenesis - has been adopted in zebrafish and successfully used to identify conserved and novel cancer genes (5). More recently, the development of efficient gene knockdown technology has transformed zebrafish into a reverse genetic system. Morpholinos - antisense oligonucleotides that inhibit translation or affect splicing -...