title: Insights from a transgenic mouse model on the role of SLC26A2 in health and disease.
abstract: Mutations in the SLC26A2 cause a family of recessive chondrodysplasias that includes in order of decreasing severity achondrogenesis 1B, atelosteogenesis 2, diastrophic dysplasia and recessive multiple epiphyseal dysplasia. The gene encodes for a widely distributed sulfate/chloride antiporter of the cell membrane whose function is crucial for the uptake of inorganic sulfate that is needed for proteoglycan sulfation. To investigate the mechanisms leading to skeletal dysplasia, we generated a transgenic mouse with a mutation in Slc26a2 causing a partial loss of function of the sulfate transporter. Homozygous mutant mice were characterized by skeletal dysplasia with chondrocytes of irregular size, delay in the formation of the secondary ossification centre and osteoporosis of long bones. Impaired sulfate uptake was demonstrated in chondrocytes, osteoblasts and fibroblasts, but proteoglycan undersulfation was detected only in cartilage. The similarity with human diastrophic dysplasia makes this mouse a model to explore pathogenetic and therapeutic aspects of SLC26A2-related disorders.
authors.affiliation: Dipartimento di Biochimica Alessandro Castellani, Università di Pavia, 1-27100 Pavia, Italy.
authors.forename: Antonella
authors.initials: A
authors.lastname: Forlino
authors.forename: Benedetta
authors.initials: B
authors.lastname: Gualeni
authors.forename: Fabio
authors.initials: F
authors.lastname: Pecora
authors.forename: Sara
authors.initials: S
authors.lastname: Della Torre
authors.forename: Rocco
authors.initials: R
authors.lastname: Piazza
authors.forename: Cecilia
authors.initials: C
authors.lastname: Tiveron
authors.forename: Laura
authors.initials: L
authors.lastname: Tatangelo
authors.forename: Andrea
authors.initials: A
authors.lastname: Superti-Furga
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Cetta
authors.forename: Antonio
authors.initials: A
authors.lastname: Rossi
mesh_terms: D000818:Animals; D027321:Anion Transport Proteins / Q000737:chemistry / Q000378:metabolism*; D019902:Chondrocytes / Q000166:cytology; D002809:Chondroitin Sulfates / Q000378:metabolism; D004195:Disease Models, Animal; D004838:Epiphyses / Q000002:abnormalities; D006262:Health; D051379:Mice; D008822:Mice, Transgenic; D000076988:Sulfate Transporters; D013431:Sulfates / Q000378:metabolism
chemical_list: D027321:Anion Transport Proteins; C513264:Slc26a2 protein, mouse; D000076988:Sulfate Transporters; D013431:Sulfates; D002809:Chondroitin Sulfates