News

A joint initiative between researchers at RIBES and Radboudumc has led to new insights into the functions of a gene that in humans is implicated in cleft palate and thyroid dysgenesis. A zebrafish mutant was generated that has a disruption in the nuclear localization signal in the foxe1 gene. Skeletal development and thyroidogenesis in these mutants were investigated, focusing on embryonic and larval stages.

Ammonia accumulation is a major challenge in intensive aquaculture, where fish are fed protein-rich diets in large rations, resulting in increased ammonia production when amino acids are metabolized as energy source. Ammonia is primarily excreted via the gills, which have been found to harbor nitrogen-cycle bacteria that convert ammonia into dinitrogen gas (N2) and therefore present a potential in situ detoxifying mechanism.A research team from Animal Physiology and Microbiology, in collaboration with Wageningen University, determined the impact of feeding strategies (demand-feeding and batch-feeding) with two dietary protein levels on growth, nitrogen excretion, and nitrogen metabolism in common carp (Cyprinus carpio, L.) in a 3-week feeding experiment. Demand-fed fish exhibited significantly higher growth rates, though with lower feed efficiency. When corrected for feed intake, nitrogen excretion was not impacted by feeding strategy or dietary protein, but demand-fed fish had significantly more nitrogen unaccounted for in the nitrogen balance and less retained nitrogen. N2 production of individual fish was measured in all experimental groups, and production rates were in the same order of magnitude as the amount of nitrogen unaccounted for, thus potentially explaining the missing nitrogen in the balance. N2 production by carp was also observed when groups of fish were kept in metabolic chambers. Demand feeding furthermore caused a significant increase in hepatic glutamate dehydrogenase activities, indicating elevated ammonia production. However, branchial ammonia transporter expression levels in these animals were stable or decreased. Together, the results suggest that feeding strategy impacts fish growth and nitrogen metabolism, and that conversion of ammonia to N2 by nitrogen cycle bacteria in the gills may explain the unaccounted nitrogen in the balance.

In the last decade, predictions of impacts of climate change on biodiversity, and how to model changes in species distributions have gained relatively more attention than the importance of understanding physiological principles of an organism in predicting its response to climate change. Therefore, we recently launched a PhD research project into the combined effects of climate change factors (thermal stress, hypoxia, acidification) on (skeletal) development in early fish developmental stages. The investigation will increase our insights in the effects and interactions of climate change-induced environmental changes on fish development and vulnerability.

The Radboud Zebrafish Facility has two new zebrafish systems that together provide space for more than 250 tanks. They are the most modern, recirculating housing systems, equipped with light blue polycarbonate tanks to prevent algae growth. The systems are also equipped with mechanical, chemical and biological filtration, UV disinfection and buffering. In this way, less stress for the animals and better fish welfare is guaranteed.

Researchers from the department of Otorhinolaryngology generated and characterized an ush2ap.(Cys771Phe) zebrafish knock-in model, mimicking human p.(Cys759Phe). They used functional and immunohistochemical analyses. Besides the homozygous c.2276 G > T USH2A variant, no alternative genetic causes were identified. Evaluation of the ush2ap.(Cys771Phe) zebrafish model revealed strongly reduced levels of usherin expression at the photoreceptor periciliary membrane, increased levels of rhodopsin localization in the photoreceptor cell body and decreased electroretinogram (ERG) b-wave amplitudes compared to wildtype controls. In conclusion, we confirmed pathogenicity of USH2A c.2276 G > T (p.(Cys759Phe)). Consequently, cases homozygous for c.2276 G > T can now receive a definite genetic diagnosis and can be considered eligible for receiving future QR-421a-mediated exon 13 skipping therapy.