Humanizing the zebrafish liver shifts drug metabolic profiles and improves pharmacokinetics of CYP3A4 substrates.

Understanding and predicting whether new drug candidates will be safe in the clinic is a critical hurdle in pharmaceutical development, that relies in part on absorption, distribution, metabolism, excretion and toxicology studies in vivo. Zebrafish is a relatively new model system for drug metabolism and toxicity studies, offering whole organism screening coupled with small size and potential for high-throughput screening. Through toxicity and absorption analyses of a number of drugs, we find that zebrafish is generally predictive of drug toxicity, although assay outcomes are influenced by drug lipophilicity which alters drug uptake.

The influence of the zebrafish genetic background on Parkinson's disease-related aspects.

Zebrafish are increasingly used to study neurodegenerative conditions such as Parkinson's disease (PD). In rodents, the influence of the genetic background on important experimental parameters in PD research such as susceptibility to toxin exposure or motor behavior is well established. In contrast, little is known about the impact of the genetic background in commonly used zebrafish wild-type strains on these important experimental parameters.

Genetic analysis of fin development in zebrafish identifies furin and hemicentin1 as potential novel fraser syndrome disease genes.

Using forward genetics, we have identified the genes mutated in two classes of zebrafish fin mutants. The mutants of the first class are characterized by defects in embryonic fin morphogenesis, which are due to mutations in a Laminin subunit or an Integrin alpha receptor, respectively. The mutants of the second class display characteristic blistering underneath the basement membrane of the fin epidermis.

Complex I deficiency and dopaminergic neuronal cell loss in parkin-deficient zebrafish (Danio rerio).

Currently, only symptomatic therapy is available for Parkinson's disease. The zebrafish is a vertebrate animal model ideally suited for high throughput compound screening to identify disease-modifying compounds for Parkinson's disease. We have developed a zebrafish model for Parkin deficiency, the most commonly mutated gene in early onset Parkinson's disease.

Zebrafish as a new animal model for movement disorders.

The zebrafish, long recognized as a model organism for the analysis of basic developmental processes, is now also emerging as an alternative animal model for human diseases. This review will first provide an overview of the particular characteristics of zebrafish in general and their dopaminergic nervous system in particular. We will then summarize all work undertaken so far to establish zebrafish as a new animal model for movement disorders and will finally emphasize its particular strength - amenability to high throughput in vivo drug screening.

p53-dependent neuronal cell death in a DJ-1-deficient zebrafish model of Parkinson's disease.

Mutations in DJ-1 lead to early onset Parkinson's disease (PD). The aim of this study was to elucidate further the underlying mechanisms leading to neuronal cell death in DJ-1 deficiency in vivo and determine whether the observed cell loss could be prevented pharmacologically. Inactivation of DJ-1 in zebrafish, Danio rerio, resulted in loss of dopaminergic neurons after exposure to hydrogen peroxide and the proteasome inhibitor MG132.

Hedgehog signalling and the specification of muscle cell identity in the zebrafish embryo.

Signalling by members of the Hedgehog family of secreted proteins plays a central role in the development of many animal species. In the zebrafish embryo, the specification of myoblast fates is controlled by Hedgehog signals emanating from axial midline structures. Distinct muscle cell identities are induced by varying levels of signalling activity.

Cloning of zebrafish T-box genes tbx15 and tbx18 and their expression during embryonic development.

Members of the T-box (tbx) gene family encode developmentally regulated transcription factors, several of which are implicated in human hereditary diseases. We have cloned the paralogous genes tbx15 and tbx18 in zebrafish and have characterised their expression in detail. tbx15 is expressed in paraxial head mesenchyme and its derivatives, the extraocular and jaw musculature and the posterior neurocranium.