2018 年 30 巻 174 号 p. E67-E89
The indispensable roles of glycosaminoglycans (GAGs), including chondroitin sulfate, dermatan sulfate, and heparan sulfate, have been demonstrated in various biological events such as construction of the extracellular matrix, tissue development, and cell signaling through interactions with extracellular matrix components, morphogens, and growth factors by analyses using the following model organisms: nematodes, fruit flies, frogs, zebrafish, and mice. A large number of human genetic diseases including heart defects, immune deficiencies, and neurological abnormalities in addition to connective tissue diseases such as hereditary multiple exostoses and Ehlers–Danlos syndrome were recently reported to be caused by mutations in the genes encoding glycosyltransferases, epimerases, and sulfotransferases that are responsible for the biosynthesis of GAGs. Glycobiological approaches revealed that mutations in GAG-biosynthetic enzymes led to reductions in their enzymatic activities as well as in the levels of GAGs. This review provides an overview of the growing number of glycobiological studies on recently characterized genetic disorders caused by the faulty biosynthesis of GAGs.
