PUBLICATION
Mutation of microphthalmia-associated transcription factor (mitf) in zebrafish sensitizes for glomerulopathy
- Authors
- Müller-Deile, J., Schenk, H., Niggemann, P., Bolaños-Palmieri, P., Teng, B., Higgs, A., Staggs, L., Haller, H., Schroder, P., Schiffer, M.
- ID
- ZDB-PUB-190206-4
- Date
- 2019
- Source
- Biology Open 8(3): (Journal)
- Registered Authors
- Keywords
- Glomerulopathy, MITF, PAN, Podocyte, Zebrafish
- MeSH Terms
- none
- PubMed
- 30718228 Full text @ Biol. Open
Citation
Müller-Deile, J., Schenk, H., Niggemann, P., Bolaños-Palmieri, P., Teng, B., Higgs, A., Staggs, L., Haller, H., Schroder, P., Schiffer, M. (2019) Mutation of microphthalmia-associated transcription factor (mitf) in zebrafish sensitizes for glomerulopathy. Biology Open. 8(3):.
Abstract
Different glomerular diseases that affect podocyte homeostasis can clinically present as nephrotic syndrome with massive proteinuria, hypoalbuminemia, hyperlipidemia and edema. Up to now no drugs that specifically target the actin cytoskeleton of podocytes are on the market and model systems for library screenings to develop anti-proteinuric drugs are of high interest. We developed a standardized proteinuria model in zebrafish using puromycin aminonucleoside (PAN) via treatment in the fish water to allow for further drug testing to develop anti-proteinuric drugs for the treatment of glomerular diseases. We noticed that fish that carry the nacre-mutation show a significantly higher susceptibility for the disruption of the glomerular filtration barrier following PAN treatment, which results in a more pronounced proteinuria phenotype. Nacre zebrafish inherit a mutation yielding a truncated version of microphthalmia-associated transcription factor/ melanogenesis associated transcription factor (mitf). We hypothesized that the nacre mutation may lead to reduced formin expression and defects in cytoskeletal rearrangement. Based on the observations in zebrafish, we carried out a PAN treatment on cultured human podocytes after knockdown with MITF siRNA causing a rearrangement of the actin cytoskeleton.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping