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Modeling of ACTN4-Based Podocytopathy Using Drosophila Nephrocytes

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Modeling of ACTN4-Based Podocytopathy Using Drosophila Nephrocytes. / Odenthal, Johanna; Dittrich, Sebastian; Ludwig, Vivian; Merz, Tim; Reitmeier, Katrin; Reusch, Björn; Höhne, Martin; Cosgun, Zülfü C; Hohenadel, Maximilian; Putnik, Jovana; Göbel, Heike; Rinschen, Markus M; Altmüller, Janine; Koehler, Sybille; Schermer, Bernhard; Benzing, Thomas; Beck, Bodo B; Brinkkötter, Paul T; Habbig, Sandra; Bartram, Malte P.

in: KIDNEY INT REP, Jahrgang 8, Nr. 2, 02.2023, S. 317-329.

Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung

Harvard

Odenthal, J, Dittrich, S, Ludwig, V, Merz, T, Reitmeier, K, Reusch, B, Höhne, M, Cosgun, ZC, Hohenadel, M, Putnik, J, Göbel, H, Rinschen, MM, Altmüller, J, Koehler, S, Schermer, B, Benzing, T, Beck, BB, Brinkkötter, PT, Habbig, S & Bartram, MP 2023, 'Modeling of ACTN4-Based Podocytopathy Using Drosophila Nephrocytes', KIDNEY INT REP, Jg. 8, Nr. 2, S. 317-329. https://doi.org/10.1016/j.ekir.2022.10.024

APA

Odenthal, J., Dittrich, S., Ludwig, V., Merz, T., Reitmeier, K., Reusch, B., Höhne, M., Cosgun, Z. C., Hohenadel, M., Putnik, J., Göbel, H., Rinschen, M. M., Altmüller, J., Koehler, S., Schermer, B., Benzing, T., Beck, B. B., Brinkkötter, P. T., Habbig, S., & Bartram, M. P. (2023). Modeling of ACTN4-Based Podocytopathy Using Drosophila Nephrocytes. KIDNEY INT REP, 8(2), 317-329. https://doi.org/10.1016/j.ekir.2022.10.024

Vancouver

Odenthal J, Dittrich S, Ludwig V, Merz T, Reitmeier K, Reusch B et al. Modeling of ACTN4-Based Podocytopathy Using Drosophila Nephrocytes. KIDNEY INT REP. 2023 Feb;8(2):317-329. https://doi.org/10.1016/j.ekir.2022.10.024

Bibtex

@article{9bedba5b81274c89a531d9c10461a3c2,
title = "Modeling of ACTN4-Based Podocytopathy Using Drosophila Nephrocytes",
abstract = "INTRODUCTION: Genetic disorders are among the most prevalent causes leading to progressive glomerular disease and, ultimately, end-stage renal disease (ESRD) in children and adolescents. Identification of underlying genetic causes is indispensable for targeted treatment strategies and counseling of affected patients and their families.METHODS: Here, we report on a boy who presented at 4 years of age with proteinuria and biopsy-proven focal segmental glomerulosclerosis (FSGS) that was temporarily responsive to treatment with ciclosporin A. Molecular genetic testing identified a novel mutation in alpha-actinin-4 (p.M240T). We describe a feasible and efficient experimental approach to test its pathogenicity by combining in silico, in vitro, and in vivo analyses.RESULTS: The de novo p.M240T mutation led to decreased alpha-actinin-4 stability as well as protein mislocalization and actin cytoskeleton rearrangements. Transgenic expression of wild-type human alpha-actinin-4 in Drosophila melanogaster nephrocytes was able to ameliorate phenotypes associated with the knockdown of endogenous actinin. In contrast, p.M240T, as well as other established disease variants p.W59R and p.K255E, failed to rescue these phenotypes, underlining the pathogenicity of the novel alpha-actinin-4 variant.CONCLUSION: Our data highlight that the newly identified alpha-actinin-4 mutation indeed encodes for a disease-causing variant of the protein and promote the Drosophila model as a simple and convenient tool to study monogenic kidney disease in vivo.",
author = "Johanna Odenthal and Sebastian Dittrich and Vivian Ludwig and Tim Merz and Katrin Reitmeier and Bj{\"o}rn Reusch and Martin H{\"o}hne and Cosgun, {Z{\"u}lf{\"u} C} and Maximilian Hohenadel and Jovana Putnik and Heike G{\"o}bel and Rinschen, {Markus M} and Janine Altm{\"u}ller and Sybille Koehler and Bernhard Schermer and Thomas Benzing and Beck, {Bodo B} and Brinkk{\"o}tter, {Paul T} and Sandra Habbig and Bartram, {Malte P}",
note = "{\textcopyright} 2022 Published by Elsevier Inc. on behalf of the International Society of Nephrology.",
year = "2023",
month = feb,
doi = "10.1016/j.ekir.2022.10.024",
language = "English",
volume = "8",
pages = "317--329",
journal = "KIDNEY INT REP",
issn = "2468-0249",
publisher = "Elsevier Inc.",
number = "2",

}

RIS

TY - JOUR

T1 - Modeling of ACTN4-Based Podocytopathy Using Drosophila Nephrocytes

AU - Odenthal, Johanna

AU - Dittrich, Sebastian

AU - Ludwig, Vivian

AU - Merz, Tim

AU - Reitmeier, Katrin

AU - Reusch, Björn

AU - Höhne, Martin

AU - Cosgun, Zülfü C

AU - Hohenadel, Maximilian

AU - Putnik, Jovana

AU - Göbel, Heike

AU - Rinschen, Markus M

AU - Altmüller, Janine

AU - Koehler, Sybille

AU - Schermer, Bernhard

AU - Benzing, Thomas

AU - Beck, Bodo B

AU - Brinkkötter, Paul T

AU - Habbig, Sandra

AU - Bartram, Malte P

N1 - © 2022 Published by Elsevier Inc. on behalf of the International Society of Nephrology.

PY - 2023/2

Y1 - 2023/2

N2 - INTRODUCTION: Genetic disorders are among the most prevalent causes leading to progressive glomerular disease and, ultimately, end-stage renal disease (ESRD) in children and adolescents. Identification of underlying genetic causes is indispensable for targeted treatment strategies and counseling of affected patients and their families.METHODS: Here, we report on a boy who presented at 4 years of age with proteinuria and biopsy-proven focal segmental glomerulosclerosis (FSGS) that was temporarily responsive to treatment with ciclosporin A. Molecular genetic testing identified a novel mutation in alpha-actinin-4 (p.M240T). We describe a feasible and efficient experimental approach to test its pathogenicity by combining in silico, in vitro, and in vivo analyses.RESULTS: The de novo p.M240T mutation led to decreased alpha-actinin-4 stability as well as protein mislocalization and actin cytoskeleton rearrangements. Transgenic expression of wild-type human alpha-actinin-4 in Drosophila melanogaster nephrocytes was able to ameliorate phenotypes associated with the knockdown of endogenous actinin. In contrast, p.M240T, as well as other established disease variants p.W59R and p.K255E, failed to rescue these phenotypes, underlining the pathogenicity of the novel alpha-actinin-4 variant.CONCLUSION: Our data highlight that the newly identified alpha-actinin-4 mutation indeed encodes for a disease-causing variant of the protein and promote the Drosophila model as a simple and convenient tool to study monogenic kidney disease in vivo.

AB - INTRODUCTION: Genetic disorders are among the most prevalent causes leading to progressive glomerular disease and, ultimately, end-stage renal disease (ESRD) in children and adolescents. Identification of underlying genetic causes is indispensable for targeted treatment strategies and counseling of affected patients and their families.METHODS: Here, we report on a boy who presented at 4 years of age with proteinuria and biopsy-proven focal segmental glomerulosclerosis (FSGS) that was temporarily responsive to treatment with ciclosporin A. Molecular genetic testing identified a novel mutation in alpha-actinin-4 (p.M240T). We describe a feasible and efficient experimental approach to test its pathogenicity by combining in silico, in vitro, and in vivo analyses.RESULTS: The de novo p.M240T mutation led to decreased alpha-actinin-4 stability as well as protein mislocalization and actin cytoskeleton rearrangements. Transgenic expression of wild-type human alpha-actinin-4 in Drosophila melanogaster nephrocytes was able to ameliorate phenotypes associated with the knockdown of endogenous actinin. In contrast, p.M240T, as well as other established disease variants p.W59R and p.K255E, failed to rescue these phenotypes, underlining the pathogenicity of the novel alpha-actinin-4 variant.CONCLUSION: Our data highlight that the newly identified alpha-actinin-4 mutation indeed encodes for a disease-causing variant of the protein and promote the Drosophila model as a simple and convenient tool to study monogenic kidney disease in vivo.

U2 - 10.1016/j.ekir.2022.10.024

DO - 10.1016/j.ekir.2022.10.024

M3 - SCORING: Journal article

C2 - 36815115

VL - 8

SP - 317

EP - 329

JO - KIDNEY INT REP

JF - KIDNEY INT REP

SN - 2468-0249

IS - 2

ER -