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Can I read Mutation-Dependent Pathomechanisms Determine the Phenotype in the Bestrophinopathies on EtoBox?
Mutation-Dependent Pathomechanisms Determine the Phenotype in the Bestrophinopathies by Anna-Lena Nachtigal; Andrea Milenkovic; Caroline Brandl; Heidi L. Schulz; Lisa M. J. Duerr; Gabriele E. Lang; Charlotte Reiff; Philipp Herrmann; Ulrich Kellner; Bernhard H.F. Weber is a Biochemistry, Genetics and Molecular Biology article available to read on EtoBox.
What is Mutation-Dependent Pathomechanisms Determine the Phenotype in the Bestrophinopathies about?
Best vitelliform macular dystrophy (BD), autosomal dominant vitreoretinochoroidopathy (ADVIRC), and the autosomal recessive bestrophinopathy (ARB), together known as the bestrophinopathies, are caused by mutations in the bestrophin-1 (__BEST1__) gene affecting anion transport through the plasma membrane of the retinal pigment epithelium (RPE). To date, while no treatment exists a better understanding of BEST1-related pathogenesis may help to define therapeutic targets. Here, we systematically characterize functional consequences of mutant BEST1 in thirteen RPE patient cell lines differentiated from human induced pluripotent stem cells (hiPSCs). Both BD and ARB hiPSC-RPEs display a strong reduction of BEST1-mediated anion transport function compared to control, while ADVIRC mutations trigger an increased anion permeability suggesting a stabilized open state condition of channel gating. Furthermore, BD and ARB hiPSC-RPEs differ by the degree of mutant protein turnover and by the site of subcellular protein quality control with adverse effects on lysosomal pH only in the BD-related cell lines. The latter finding is consistent with an altered processing of catalytic enzymes in the lyso
Who reads Mutation-Dependent Pathomechanisms Determine the Phenotype in the Bestrophinopathies?
It is typically read by researchers, students, and practitioners in Biochemistry, Genetics and Molecular Biology.
- Author
- Anna-Lena Nachtigal; Andrea Milenkovic; Caroline Brandl; Heidi L. Schulz; Lisa M. J. Duerr; Gabriele E. Lang; Charlotte Reiff; Philipp Herrmann; Ulrich Kellner; Bernhard H.F. Weber
- Publisher
- Molecular Diversity Preservation International; MDPI AG; Multidisciplinary Digital Publishing Institute (MDPI); Basel: MDPI Center, 2000- (ISSN 1422-0067)
- Published
- 2020
- Language
- EN
- Field
- Biochemistry, Genetics and Molecular Biology (Life Sciences)