Dysfunctional Mitochondria in Cardiac Fibers of a Williams-Beuren Syndrome Mouse Model

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2023, Volume and Issue: unknown

Published: May 15, 2023

Summary Williams-Beuren Syndrome (WBS) is a rare neurodevelopmental disorder that, together with rather characteristic neurocognitive profile, presents strong cardiovascular phenotype. The features of WBS are mainly related to gene dosage effect due hemizygosity the elastin ( ELN ) gene; however, phenotypic variability between patients indicates presence important modulators clinical impact deficiency. Recently, two genes within region have been linked mitochondrial dysfunction. Numerous diseases dysfunction; therefore, it could be modulator phenotype present in WBS. Here, we analyze function and dynamics cardiac tissue from complete deletion (CD) model. Our research reveals that fiber mitochondria CD animals altered dynamics, accompanied by respiratory chain dysfunction decreased ATP production, reproducing alterations observed fibroblasts patients. results highlight major factors; on one hand, probably relevant mechanism underlying several risk factors associated disease; other, murine model mimics great for carrying out preclinical tests drugs targeting mitochondria.

Language: Английский

Dysfunctional Mitochondria in the Cardiac Fibers of a Williams–Beuren Syndrome Mouse Model

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(12), P. 10071 - 10071

Published: June 13, 2023

Williams-Beuren syndrome (WBS) is a rare neurodevelopmental disorder that, together with rather characteristic neurocognitive profile, presents strong cardiovascular phenotype. The features of WBS are mainly related to gene dosage effect due hemizygosity the elastin (ELN) gene; however, phenotypic variability between patients indicates presence important modulators clinical impact deficiency. Recently, two genes within region have been linked mitochondrial dysfunction. Numerous diseases dysfunction; therefore, it could be modulator phenotype present in WBS. Here, we analyze function and dynamics cardiac tissue from complete deletion (CD) model. Our research reveals that fiber mitochondria CD animals altered dynamics, accompanied by respiratory chain dysfunction decreased ATP production, reproducing alterations observed fibroblasts patients. results highlight major factors: on one hand, probably relevant mechanism underlying several risk factors associated disease; other, murine model mimics great for carrying out preclinical tests drugs targeting mitochondria.

Language: Английский