Validation of metaxin-2 deficient C. elegans as a model for MandibuloAcral Dysplasia associated to mtx-2 (MADaM) syndrome.

Chloé Talarmin-Gas, Georges Smolyakov, Cleo Parisi, Cyril Scandola, Valérie Andrianasolonirina, Cloé Lecoq, Valentine Houtart, Song-Hua Lee, Homa Adle-Biassette, Bénédicte Thiébot, Timothy Ganderton, Philippe Manivet

Université Paris Cité, INSERM UMR 1141 "NeuroDiderot", FHU Iio2-D2, Paris, France. [email protected]é Paris Cité, INSERM UMR 1141 "NeuroDiderot", FHU Iio2-D2, Paris, France. [email protected]. · pubmed

Paper

Abstract

MandibuloAcral Dysplasia associated to MTX2 gene (MADaM) is a recently described progeroid syndrome (accelerated aging disease) whose clinical manifestations include skin abnormalities, growth retardation, and cardiovascular diseases. We previously proposed that mtx-2-deficient C. elegans could be used as a model for MADaM and to support this, we present here our comprehensive phenotypic characterization of these worms using atomic force microscopy (AFM), transcriptomic, and oxygen consumption rate analyses. AFM analysis showed that young mtx-2-less worms had a significantly rougher, less elastic cuticle which becomes significantly rougher and less elastic as they age, and abnormal mitochondrial morphology. mtx-2 C. elegans displayed slightly delayed development, decreased pharyngeal pumping, significantly reduced mitochondrial respiratory capacities, and transcriptomic analysis identified perturbations in the aging, TOR, and WNT-signaling pathways. The phenotypic characteristics of mtx-2 worms shown here are analogous to many of the human clinical presentations of MADaM and we believe this validates their use as a model which will allow us to uncover the molecular details of the disease and develop new therapeutics and treatments.

The following analysis is generated by AI and may contain errors. It is separate from the authors’ abstract and is not peer review.

Research summary

The paper presents a model for MandibuloAcral Dysplasia associated with the MTX2 gene, which is linked to progeroid syndromes and accelerated aging. While it explores the phenotypic characteristics of a model organism that may help in understanding the molecular details of the disease, the focus is primarily on validating a model rather than addressing the root causes of aging or developing broad lifespan extension strategies. Thus, while it contributes to the understanding of a specific aging-related condition, its overall impact on the field of longevity research is limited.

Author of this paper? Send a correction.