Transcriptomic analysis of gene expression pathways impacted by metaxin-2 (MTX-2) deficiency in a C. elegans mutant (mtx-2 KO, (gk444)) vs Wild-type worms (N2 Bristol)

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 delayed development, decreased pharyngeal pumping, significantly reduced mitochondrial respiratory capacities, and transcriptomics 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. To investigate the different genes expressed in the nematode C. elegans due to the absence of the mtx-2 gene (an outer mitochondrial membrane gene). We performed gene expression profiling analysis using data obtained from triplicate samples of RNA-Seq of mutant worms (mtx-2 KO, gk444), at L4 stage compared to Wild-type worms (N2 Bristol).