Article: article from journal or magazin.
The zinc transporter SLC39A13/ZIP13 is required for connective tissue development; its involvement in BMP/TGF-beta signaling pathways.
Publication types: Case Reports ; Journal Article ; Research Support, Non-U.S. Gov't
BACKGROUND: Zinc (Zn) is an essential trace element and it is abundant in connective tissues, however biological roles of Zn and its transporters in those tissues and cells remain unknown. METHODOLOGY/PRINCIPAL FINDINGS: Here we report that mice deficient in Zn transporter Slc39a13/Zip13 show changes in bone, teeth and connective tissue reminiscent of the clinical spectrum of human Ehlers-Danlos syndrome (EDS). The Slc39a13 knockout (Slc39a13-KO) mice show defects in the maturation of osteoblasts, chondrocytes, odontoblasts, and fibroblasts. In the corresponding tissues and cells, impairment in bone morphogenic protein (BMP) and TGF-beta signaling were observed. Homozygosity for a SLC39A13 loss of function mutation was detected in sibs affected by a unique variant of EDS that recapitulates the phenotype observed in Slc39a13-KO mice. CONCLUSIONS/SIGNIFICANCE: Hence, our results reveal a crucial role of SLC39A13/ZIP13 in connective tissue development at least in part due to its involvement in the BMP/TGF-beta signaling pathways. The Slc39a13-KO mouse represents a novel animal model linking zinc metabolism, BMP/TGF-beta signaling and connective tissue dysfunction.
Adolescent, Amino Acid Sequence, Animals, Bone Morphogenetic Proteins, Cation Transport Proteins, Cells, Cultured, Connective Tissue, DNA Mutational Analysis, Ehlers-Danlos Syndrome, Humans, Mice, Mice, Knockout, Models, Biological, Molecular Sequence Data, Morphogenesis, Osteogenesis, Pedigree, Sequence Homology, Amino Acid, Signal Transduction, Transforming Growth Factor beta, Young Adult, Zinc
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