Mice lacking nucleotide sugar transporter SLC35A3 exhibit lethal chondrodysplasia with vertebral anomalies and impaired glycosaminoglycan biosynthesis. 2023

Soichiro Saito, and Shuji Mizumoto, and Tsukasa Yonekura, and Rina Yamashita, and Kenta Nakano, and Tadashi Okubo, and Shuhei Yamada, and Tadashi Okamura, and Tatsuya Furuichi
Laboratory of Laboratory Animal Science and Medicine, Co-Department of Veterinary Medicine, Faculty of Agriculture, Iwate University, Morioka, Iwate, Japan.

SLC35A3 is considered an uridine diphosphate N-acetylglucosamine (UDP-GlcNAc) transporter in mammals and regulates the branching of N-glycans. A missense mutation in SLC35A3 causes complex vertebral malformation (CVM) in cattle. However, the biological functions of SLC35A3 have not been fully clarified. To address these issues, we have established Slc35a3-/-mice using CRISPR/Cas9 genome editing system. The generated mutant mice were perinatal lethal and exhibited chondrodysplasia recapitulating CVM-like vertebral anomalies. During embryogenesis, Slc35a3 mRNA was expressed in the presomitic mesoderm of wild-type mice, suggesting that SLC35A3 transports UDP-GlcNAc used for the sugar modification that is essential for somite formation. In the growth plate cartilage of Slc35a3-/-embryos, extracellular space was drastically reduced, and many flat proliferative chondrocytes were reshaped. Proliferation, apoptosis and differentiation were not affected in the chondrocytes of Slc35a3-/-mice, suggesting that the chondrodysplasia phenotypes were mainly caused by the abnormal extracellular matrix quality. Because these histological abnormalities were similar to those observed in several mutant mice accompanying the impaired glycosaminoglycan (GAG) biosynthesis, GAG levels were measured in the spine and limbs of Slc35a3-/-mice using disaccharide composition analysis. Compared with control mice, the amounts of heparan sulfate, keratan sulfate, and chondroitin sulfate/dermatan sulfate, were significantly decreased in Slc35a3-/-mice. These findings suggest that SLC35A3 regulates GAG biosynthesis and the chondrodysplasia phenotypes were partially caused by the decreased GAG synthesis. Hence, Slc35a3-/- mice would be a useful model for investigating the in vivo roles of SLC35A3 and the pathological mechanisms of SLC35A3-associated diseases.

UI MeSH Term Description Entries
D007632 Keratan Sulfate A sulfated mucopolysaccharide initially isolated from bovine cornea. At least two types are known. Type I, found mostly in the cornea, contains D-galactose and D-glucosamine-6-O-sulfate as the repeating unit; type II, found in skeletal tissues, contains D-galactose and D-galactosamine-6-O-sulfate as the repeating unit. Keratosulfate,Sulfate, Keratan
D008322 Mammals Warm-blooded vertebrate animals belonging to the class Mammalia, including all that possess hair and suckle their young. Mammalia,Mammal
D009139 Musculoskeletal Abnormalities Congenital structural abnormalities and deformities of the musculoskeletal system. Abnormalities, Musculoskeletal,Abnormality, Musculoskeletal,Musculoskeletal Abnormality
D009711 Nucleotides The monomeric units from which DNA or RNA polymers are constructed. They consist of a purine or pyrimidine base, a pentose sugar, and a phosphate group. (From King & Stansfield, A Dictionary of Genetics, 4th ed) Nucleotide
D010009 Osteochondrodysplasias Abnormal development of cartilage and bone. Dyschondroplasias,Hyperostosis Corticalis Generalisata,Melnick-Needles Syndrome,Multiple Epiphyseal Dysplasia,Schwartz-Jampel Syndrome,Spondyloepiphyseal Dysplasia,Chondrodystrophic Myotonia,Dyschondroplasia,Endosteal Hyperostosis, Autosomal Recessive,Hyperphosphatasemia Tarda,Late-Onset Spondyloepiphyseal Dysplasia,Melnick-Needles Osteodysplasty,Myotonic Chondrodystrophy,Myotonic Myopathy, Dwarfism, Chondrodystrophy, And Ocular And Facial Abnormalities,Osteodysplasty of Melnick and Needles,SED Tarda,SJA Syndrome,Schwartz Jampel Aberfeld syndrome,Schwartz-Jampel Syndrome, Type 1,Schwartz-Jampel-Aberfeld Syndrome,Sost Sclerosing Bone Dysplasia,Sost-Related Sclerosing Bone Dysplasia,Spondylo-Epimetaphyseal Dysplasia With Myotonia,Spondyloepiphyseal Dysplasia Tarda, X-Linked,Spondyloepiphyseal Dysplasia, Late,Van Buchem Disease,X-Linked SED,X-Linked SEDT,X-Linked Spondyloepiphyseal Dysplasia Tarda,Chondrodystrophy, Myotonic,Dysplasia, Spondyloepiphyseal,Late Onset Spondyloepiphyseal Dysplasia,Late Spondyloepiphyseal Dysplasia,Melnick Needles Osteodysplasty,Melnick Needles Syndrome,Myotonia, Chondrodystrophic,Osteochondrodysplasia,Osteodysplasty, Melnick-Needles,SED, X-Linked,SEDT, X-Linked,Schwartz Jampel Syndrome,Schwartz Jampel Syndrome, Type 1,Spondyloepiphyseal Dysplasia Tarda, X Linked,Spondyloepiphyseal Dysplasia, Late-Onset,Syndrome, Schwartz-Jampel-Aberfeld,X Linked SED,X Linked SEDT,X Linked Spondyloepiphyseal Dysplasia Tarda
D002417 Cattle Domesticated bovine animals of the genus Bos, usually kept on a farm or ranch and used for the production of meat or dairy products or for heavy labor. Beef Cow,Bos grunniens,Bos indicus,Bos indicus Cattle,Bos taurus,Cow,Cow, Domestic,Dairy Cow,Holstein Cow,Indicine Cattle,Taurine Cattle,Taurus Cattle,Yak,Zebu,Beef Cows,Bos indicus Cattles,Cattle, Bos indicus,Cattle, Indicine,Cattle, Taurine,Cattle, Taurus,Cattles, Bos indicus,Cattles, Indicine,Cattles, Taurine,Cattles, Taurus,Cow, Beef,Cow, Dairy,Cow, Holstein,Cows,Dairy Cows,Domestic Cow,Domestic Cows,Indicine Cattles,Taurine Cattles,Taurus Cattles,Yaks,Zebus
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D001692 Biological Transport The movement of materials (including biochemical substances and drugs) through a biological system at the cellular level. The transport can be across cell membranes and epithelial layers. It also can occur within intracellular compartments and extracellular compartments. Transport, Biological,Biologic Transport,Transport, Biologic
D014530 Uridine Diphosphate A uracil nucleotide containing a pyrophosphate group esterified to C5 of the sugar moiety. UDP,Uridine Pyrophosphate,Diphosphate, Uridine,Pyrophosphate, Uridine
D051379 Mice The common name for the genus Mus. Mice, House,Mus,Mus musculus,Mice, Laboratory,Mouse,Mouse, House,Mouse, Laboratory,Mouse, Swiss,Mus domesticus,Mus musculus domesticus,Swiss Mice,House Mice,House Mouse,Laboratory Mice,Laboratory Mouse,Mice, Swiss,Swiss Mouse,domesticus, Mus musculus

Related Publications

Soichiro Saito, and Shuji Mizumoto, and Tsukasa Yonekura, and Rina Yamashita, and Kenta Nakano, and Tadashi Okubo, and Shuhei Yamada, and Tadashi Okamura, and Tatsuya Furuichi
December 1975, Annals of the rheumatic diseases,
Soichiro Saito, and Shuji Mizumoto, and Tsukasa Yonekura, and Rina Yamashita, and Kenta Nakano, and Tadashi Okubo, and Shuhei Yamada, and Tadashi Okamura, and Tatsuya Furuichi
November 2020, The Journal of biological chemistry,
Soichiro Saito, and Shuji Mizumoto, and Tsukasa Yonekura, and Rina Yamashita, and Kenta Nakano, and Tadashi Okubo, and Shuhei Yamada, and Tadashi Okamura, and Tatsuya Furuichi
January 1970, Exposes annuels de biochimie medicale,
Soichiro Saito, and Shuji Mizumoto, and Tsukasa Yonekura, and Rina Yamashita, and Kenta Nakano, and Tadashi Okubo, and Shuhei Yamada, and Tadashi Okamura, and Tatsuya Furuichi
January 2001, American journal of medical genetics,
Soichiro Saito, and Shuji Mizumoto, and Tsukasa Yonekura, and Rina Yamashita, and Kenta Nakano, and Tadashi Okubo, and Shuhei Yamada, and Tadashi Okamura, and Tatsuya Furuichi
May 2004, Molecular and cellular biology,
Soichiro Saito, and Shuji Mizumoto, and Tsukasa Yonekura, and Rina Yamashita, and Kenta Nakano, and Tadashi Okubo, and Shuhei Yamada, and Tadashi Okamura, and Tatsuya Furuichi
March 2011, Proceedings of the National Academy of Sciences of the United States of America,
Soichiro Saito, and Shuji Mizumoto, and Tsukasa Yonekura, and Rina Yamashita, and Kenta Nakano, and Tadashi Okubo, and Shuhei Yamada, and Tadashi Okamura, and Tatsuya Furuichi
February 1985, Clinical genetics,
Soichiro Saito, and Shuji Mizumoto, and Tsukasa Yonekura, and Rina Yamashita, and Kenta Nakano, and Tadashi Okubo, and Shuhei Yamada, and Tadashi Okamura, and Tatsuya Furuichi
July 2013, The Journal of biological chemistry,
Soichiro Saito, and Shuji Mizumoto, and Tsukasa Yonekura, and Rina Yamashita, and Kenta Nakano, and Tadashi Okubo, and Shuhei Yamada, and Tadashi Okamura, and Tatsuya Furuichi
September 2018, Nature communications,
Soichiro Saito, and Shuji Mizumoto, and Tsukasa Yonekura, and Rina Yamashita, and Kenta Nakano, and Tadashi Okubo, and Shuhei Yamada, and Tadashi Okamura, and Tatsuya Furuichi
January 2019, Computational and structural biotechnology journal,
Copied contents to your clipboard!