The use of in vivo zebrafish assays in drug toxicity screening.

Anecdotal evidence has long suggested that zebrafish may be a good model to predict toxicity of human drugs. As summarized in this review, several groups have recently conducted systematic evaluations of zebrafish toxicity end points using large numbers of pharmacologically relevant compounds. Assays of particular interest include those for cardiotoxicity, ototoxicity, seizure liability, developmental toxicity and gastrointestinal motility.

In vivo imaging of zebrafish digestive organ function using multiple quenched fluorescent reporters.

Optical clarity of larvae makes the zebrafish ideal for real-time analyses of vertebrate organ function through the use of fluorescent reporters of enzymatic activities. A key function of digestive organs is to couple the generation of enzymes with mechanical processes that enable nutrient availability and absorption. However, it has been extremely difficult, and in many cases not possible, to directly observe digestive processes in a live vertebrate.

Automated, quantitative screening assay for antiangiogenic compounds using transgenic zebrafish.

Pathologic angiogenesis has emerged as an important therapeutic target in several major diseases. Zebrafish offer the potential for high-throughput drug discovery in a whole vertebrate system. We developed the first quantitative, automated assay for antiangiogenic compound identification using zebrafish embryos.

Zebrafish assays for drug toxicity screening.

Zebrafish are vertebrate organisms that are of growing interest for preclinical drug discovery applications. Zebrafish embryos develop most of the major organ systems present in mammals, including the cardiovascular, nervous and digestive systems, in < 1 week. Additional characteristics that make them advantageous for compound screening are their small size, transparency and ability to absorb compounds through the water.

Neuroprotection of MPTP-induced toxicity in zebrafish dopaminergic neurons.

Parkinson's disease is characterized by a severe loss of dopaminergic neurons resulting in a range of motor deficits. The neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) is known to cause a similar loss of dopaminergic neurons in the human midbrain with corresponding Parkinsonian symptoms. Several animal species have also shown sensitivity to MPTP, including primates, mice, goldfish, and, most recently, zebrafish.

Zebrafish: from disease modeling to drug discovery.

The study of zebrafish, a leading model organism for developmental biology, is rapidly expanding to include human disease. Zebrafish models based on known disease mechanisms have been developed in several therapeutic areas, including blood diseases, diabetes, muscular dystrophy, neurodegenerative disease, angiogenesis and lipid metabolism. This review summarizes recent progress in disease model development, and outlines the potential of zebrafish to contribute to drug discovery through the identification of novel drug targets, validation of those targets and screening for new therapeutic compounds.