<i>MFSD12</i> depletion reduces cystine accumulation without improvement in proximal tubular function in experimental models for cystinosis-Reference-Cited by-同舟云学术

MFSD12 depletion reduces cystine accumulation without improvement in proximal tubular function in experimental models for cystinosis

Published:2024-06-01 Issue:6 Volume:326 Page:F981-F987
ISSN:1931-857X
Container-title:American Journal of Physiology-Renal Physiology
language:en
Short-container-title:American Journal of Physiology-Renal Physiology

Author:

Bondue Tjessa¹^ORCID,Khodaparast Laleh²³,Khodaparast Ladan²³^ORCID,Cairoli Sara⁴^ORCID,Goffredo Bianca Maria⁴,Gijsbers Rik⁵⁶,van den Heuvel Lambertus¹⁷,Levtchenko Elena¹⁸^ORCID

Affiliation:

1. Laboratory of Pediatric Nephrology, Department of Development and Regeneration, KU Leuven, Leuven, Belgium

2. Switch Laboratory, VIB Center for Brain and Disease Research, Leuven, Belgium

3. Switch Laboratory, Department of Cellular and Molecular Medicine, KU Leuven, Leuven, Belgium

4. Laboratory of Metabolic Biochemistry, Department of Pediatric Medicine, Bambino Gesù Children’s Hospital, IRCCS, Rome, Italy

5. Laboratory for Molecular Virology and Gene Therapy, Department of Pharmaceutical and Pharmacological Sciences, KU Leuven, Leuven, Belgium

6. Leuven Viral Vector Core, KU Leuven, Leuven, Belgium

7. Department of Pediatric Nephrology, Radboud University Medical Center, Nijmegen, The Netherlands

8. Department of Pediatric Nephrology, Emma Children’s Hospital, Amsterdam UMC, Amsterdam, The Netherlands

Abstract

In this study, we show that MFSD12 depletion with either CRISPR/Cas9-mediated gene editing or a translation-blocking morpholino significantly reduced cystine levels in cystinosis ciPTECs and ctns−/− zebrafish embryos, respectively. However, we observed no improvement in the proximal tubular reabsorption of dextran in the ctns−/− zebrafish embryos injected with mfsd12a translation-blocking morpholino. Furthermore, a negative effect of the mfsd12a morpholino on the zebrafish development warrants further investigation.

Funder

Cystinosis Ireland and the Cystinosis Foundation UK co-funded Research Award 2021

Fonds Wetenschappelijk Onderzoek

KU Leuven

Publisher

American Physiological Society

Link

https://journals.physiology.org/doi/pdf/10.1152/ajprenal.00014.2024

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