CANT1 DEFICIENCY ALTERS THE EXPRESSION OF GENES INVOLVED IN GAG BIOSYNTHESIS AND GOLGI FUNCTION IN A MOUSE MODEL OF DESBUQUOIS DYSPLASIA TYPE 1

Desbuquois Dysplasia Type 1 (DBQD1) is a rare autosomal recessive chondrodysplasia resulting from mutations in the CANT1 gene, which encodes the calcium-activated nucleotidase 1 enzyme found in the Golgi apparatus. Cant1 is known to hydrolyze UDP, a byproduct of the reactions catalyzed by glycosyltransferases during the synthesis of glycosaminoglycans (GAGs), the oligosaccharide part of proteoglycans. In this study, we investigated the effects of Cant1 gene deletion on glycosaminoglycan synthesis in cartilage using a knock-out murine model. Our objective was to assess changes in the expression of selected genes involved in the enzymatic and regulatory pathways of GAG biosynthesis, with a particular focus on chondroitin sulfate. Our data revealed altered expression levels of genes encoding structural proteins, glycosyltransferases, and enzymes responsible for glycosylation and chondroitin sulfate sulfation in the cartilage of knockout mice compared to wild-types. Notably, GCP60, a protein associated with Golgi structure, exhibited differential expression in the knockout, suggesting potential changes in the Golgi function that may impact GAG processing and secretion. Furthermore, we observed increased protein levels of GM130, a structural component of Golgi apparatus, and of Golgin97, a protein implicated in Golgi-mediated vesicular trafficking. All these data indicate that the Golgi apparatus undergoes structural and functional modifications. Thus, the loss of CANT1 may modulate the expression of genes involved in GAG biosynthesis and in Golgi organization and function. However, further studies are required to elucidate the underlying molecular mechanisms and to better define the specific contributions of these genes to the observed phenotype. Acknowledge. This research was founded by European Union (PRIN_2022ETJJES_003)