PUBLICATION
A novel zebrafish luminescent biosensor for kidney tubulopathy, metal toxicity, and drug screening
- Authors
- Lai, H., Goldade, M., Keller, S.A., Worms, I., Luciani, A., Neuhauss, S.C.F., Slaveykova, V.I., Devuyst, O., Chen, Z.
- ID
- ZDB-PUB-260407-13
- Date
- 2026
- Source
- Disease models & mechanisms : (Journal)
- Registered Authors
- Chen, Zhiyong, Devuyst, Oliver, Goldade, Monica, Keller, Svenja, Lai, Han, Luciani, Alessandro, Neuhauss, Stephan
- Keywords
- Low-molecular-weight proteinuria, Lysosome, NanoLuc luciferase, Proximal tubule, Receptor-mediated endocytosis
- MeSH Terms
- none
- PubMed
- 41943637 Full text @ Dis. Model. Mech.
Citation
Lai, H., Goldade, M., Keller, S.A., Worms, I., Luciani, A., Neuhauss, S.C.F., Slaveykova, V.I., Devuyst, O., Chen, Z. (2026) A novel zebrafish luminescent biosensor for kidney tubulopathy, metal toxicity, and drug screening. Disease models & mechanisms. :.
Abstract
An efficient endolysosomal pathway is crucial to mediate the reabsorption and processing of ultrafiltered solutes including low-molecular-weight (LMW) proteins by epithelial cells lining the proximal tubule (PT) of the kidney. The zebrafish pronephros is used as a model system for congenital or acquired disorders that impair endolysosomal processing in PT cells, causing an inappropriate loss of solutes and LMW proteins in urine. Here, we describe a new reporter ½vdbp-NanoLuc zebrafish line, in which vitamin D-binding protein is coupled to NanoLuc luciferase for detection of PT dysfunction and LMW proteinuria. We demonstrate the reliability and value of the ½vdbp-NanoLuc biosensor in fish models of monogenic endolysosomal diseases, gentamicin and cisplatin-induced nephrotoxicity, and metal contamination. This novel reporter system yields mechanistic insights into cadmium- and copper-induced PT dysfunction and provides a platform for drug screening.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping