Mutation of microphthalmia-associated transcription factor (mitf) in zebrafish sensitizes for glomerulopathy

Müller-Deile J, Schenk H, Niggemann P, Bolanõs-Palmieri P, Teng B, Higgs A, Staggs L, Haller H, Schroder P, Schiffer M (2019)

Publication Type: Journal article

Publication year: 2019

Journal

Biology Open Company of Biologists: OAJ / Company of Biologists

Book Volume: 8

Article Number: bio040253

Journal Issue: 3

DOI: 10.1242/bio.040253

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.

Authors with CRIS profile

Janina Müller-Deile
Mario Schiffer Lehrstuhl für Innere Medizin IV

Involved external institutions

Medizinische Hochschule Hannover (MHH) / Hannover Medical School DE Germany (DE) Mount Desert Island Biological Laboratory US United States (USA) (US)

How to cite

APA:

Müller-Deile, J., Schenk, H., Niggemann, P., Bolanõs-Palmieri, P., Teng, B., Higgs, A.,... Schiffer, M. (2019). Mutation of microphthalmia-associated transcription factor (mitf) in zebrafish sensitizes for glomerulopathy. Biology Open, 8(3). https://dx.doi.org/10.1242/bio.040253

MLA:

Müller-Deile, Janina, et al. "Mutation of microphthalmia-associated transcription factor (mitf) in zebrafish sensitizes for glomerulopathy." Biology Open 8.3 (2019).

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