title: Human genetic disorders and knockout mice deficient in glycosaminoglycan.
abstract: Glycosaminoglycans (GAGs) are constructed through the stepwise addition of respective monosaccharides by various glycosyltransferases and maturated by epimerases and sulfotransferases. The structural diversity of GAG polysaccharides, including their sulfation patterns and sequential arrangements, is essential for a wide range of biological activities such as cell signaling, cell proliferation, tissue morphogenesis, and interactions with various growth factors. Studies using knockout mice of enzymes responsible for the biosynthesis of the GAG side chains of proteoglycans have revealed their physiological functions. Furthermore, mutations in the human genes encoding glycosyltransferases, sulfotransferases, and related enzymes responsible for the biosynthesis of GAGs cause a number of genetic disorders including chondrodysplasia, spondyloepiphyseal dysplasia, and Ehlers-Danlos syndromes. This review focused on the increasing number of glycobiological studies on knockout mice and genetic diseases caused by disturbances in the biosynthetic enzymes for GAGs.
authors.affiliation: Department of Pathobiochemistry, Faculty of Pharmacy, Meijo University, 150 Yagotoyama, Tempaku-ku, Nagoya 468-8503, Japan.
authors.forename: Shuji
authors.identifier: 0000-0002-4641-1505
authors.initials: S
authors.lastname: Mizumoto
authors.affiliation: Department of Pathobiochemistry, Faculty of Pharmacy, Meijo University, 150 Yagotoyama, Tempaku-ku, Nagoya 468-8503, Japan.
authors.forename: Shuhei
authors.identifier: 0000-0002-1284-9795
authors.initials: S
authors.lastname: Yamada
authors.affiliation: Laboratory of Proteoglycan Signaling and Therapeutics, Frontier Research Center for Post-Genomic Science and Technology, Graduate School of Life Science, Hokkaido University, West-11, North-21, Kita-ku, Sapporo, Hokkaido 001-0021, Japan.
authors.forename: Kazuyuki
authors.identifier: 0000-0003-3600-9376
authors.initials: K
authors.lastname: Sugahara
mesh_terms: D000818:Animals; D049109:Cell Proliferation; D004535:Ehlers-Danlos Syndrome / Q000235:genetics* / Q000473:pathology; D006025:Glycosaminoglycans / Q000096:biosynthesis / Q000235:genetics*; D016695:Glycosyltransferases / Q000235:genetics*; D006801:Humans; D018345:Mice, Knockout; D009024:Morphogenesis / Q000235:genetics; D009154:Mutation; D010009:Osteochondrodysplasias / Q000235:genetics* / Q000473:pathology; D015398:Signal Transduction
chemical_list: D006025:Glycosaminoglycans; D016695:Glycosyltransferases