title: The zinc transporter SLC39A13/ZIP13 is required for connective tissue development; its involvement in BMP/TGF-beta signaling pathways.
abstract: 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.
  
  
  RESULTS
  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
  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.
authors.affiliation: Laboratory for Cytokine Signaling, RIKEN Research Center for Allergy and Immunology, Tsurumi, Yokohama, Kanagawa, Japan.
authors.forename: Toshiyuki
authors.initials: T
authors.lastname: Fukada
authors.forename: Natacha
authors.initials: N
authors.lastname: Civic
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Furuichi
authors.forename: Shinji
authors.initials: S
authors.lastname: Shimoda
authors.forename: Kenji
authors.initials: K
authors.lastname: Mishima
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Higashiyama
authors.forename: Yayoi
authors.initials: Y
authors.lastname: Idaira
authors.forename: Yoshinobu
authors.initials: Y
authors.lastname: Asada
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Kitamura
authors.forename: Satoru
authors.initials: S
authors.lastname: Yamasaki
authors.forename: Shintaro
authors.initials: S
authors.lastname: Hojyo
authors.forename: Manabu
authors.initials: M
authors.lastname: Nakayama
authors.forename: Osamu
authors.initials: O
authors.lastname: Ohara
authors.forename: Haruhiko
authors.initials: H
authors.lastname: Koseki
authors.forename: Heloisa G
authors.initials: HG
authors.lastname: Dos Santos
authors.forename: Luisa
authors.initials: L
authors.lastname: Bonafe
authors.forename: Russia
authors.initials: R
authors.lastname: Ha-Vinh
authors.forename: Andreas
authors.initials: A
authors.lastname: Zankl
authors.forename: Sheila
authors.initials: S
authors.lastname: Unger
authors.forename: Marius E
authors.initials: ME
authors.lastname: Kraenzlin
authors.forename: Jacques S
authors.initials: JS
authors.lastname: Beckmann
authors.forename: Ichiro
authors.initials: I
authors.lastname: Saito
authors.forename: Carlo
authors.initials: C
authors.lastname: Rivolta
authors.forename: Shiro
authors.initials: S
authors.lastname: Ikegawa
authors.forename: Andrea
authors.initials: A
authors.lastname: Superti-Furga
authors.forename: Toshio
authors.initials: T
authors.lastname: Hirano
mesh_terms: D000293:Adolescent; D000595:Amino Acid Sequence; D000818:Animals; D019485:Bone Morphogenetic Proteins / Q000502:physiology*; D027682:Cation Transport Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D002478:Cells, Cultured; D003238:Connective Tissue / Q000254:growth & development* / Q000378:metabolism; D004252:DNA Mutational Analysis; D004535:Ehlers-Danlos Syndrome / Q000235:genetics; D006801:Humans; D051379:Mice; D018345:Mice, Knockout; D008954:Models, Biological; D008969:Molecular Sequence Data; D009024:Morphogenesis / Q000235:genetics; D010012:Osteogenesis / Q000235:genetics; D010375:Pedigree; D017386:Sequence Homology, Amino Acid; D015398:Signal Transduction / Q000235:genetics / Q000502:physiology; D016212:Transforming Growth Factor beta / Q000502:physiology*; D055815:Young Adult; D015032:Zinc / Q000378:metabolism
chemical_list: D019485:Bone Morphogenetic Proteins; D027682:Cation Transport Proteins; C521172:SLC39A13 protein, human; D016212:Transforming Growth Factor beta; D015032:Zinc