Zebrafish as a model for study of developmental origins of chronic lung diseases

There is an evident need for new animal models to understand molecular mechanisms underlying development of chronic lung diseases, such as asthma and COPD. Recently, zebrafish (Danio rerio) has emerged as a model for various aspects of lung disease (inflammation, acute lung injury and effects of cigarette smoke). The overall aim is to establish the zebrafish as a model to study developmental origins of chronic lung disease and their transgenerational inheritance. The objective of this study was to investigate effects of nicotine on zebrafish development, selected gene expression and neutrophil chemotaxis in order to validate its usefulness as a transgenerational model. Zebrafish Tubingen wild type and Tg(mpx:GFP), were maintained and bread according to ZFbook. Toxicity of different nicotine concentrations was assessed by the analysis of survival, hatching and malformations. Real-time PCR was used to analyse expression of CYP1A1 and AHR1 genes and neutrophil counts and migration were analysed and recorded by live imaging. There was increased mortality in groups treated with 20µg/mL nicotine. An increase in malformations was present from concentration of 10µg/mL (pericardial oedema, body curvature, shortening of body and decreased movements and swim bladder inflation). The expression of CYP1A1 was observed to be increased. There was an increase of number of neutrophils and they migrated from circulation after treatment with nicotine. There is a correlation between the effects of nicotine on mammalian organisms and zebrafish. These results indicate usefulness zebrafish as a model for various aspects of chronic lung diseases. In future studies we will analyse the effect of nicotine on subsequent generations.