PLoS ONE (Jan 2008)

The zinc transporter SLC39A13/ZIP13 is required for connective tissue development; its involvement in BMP/TGF-beta signaling pathways.

  • Toshiyuki Fukada,
  • Natacha Civic,
  • Tatsuya Furuichi,
  • Shinji Shimoda,
  • Kenji Mishima,
  • Hiroyuki Higashiyama,
  • Yayoi Idaira,
  • Yoshinobu Asada,
  • Hiroshi Kitamura,
  • Satoru Yamasaki,
  • Shintaro Hojyo,
  • Manabu Nakayama,
  • Osamu Ohara,
  • Haruhiko Koseki,
  • Heloisa G Dos Santos,
  • Luisa Bonafe,
  • Russia Ha-Vinh,
  • Andreas Zankl,
  • Sheila Unger,
  • Marius E Kraenzlin,
  • Jacques S Beckmann,
  • Ichiro Saito,
  • Carlo Rivolta,
  • Shiro Ikegawa,
  • Andrea Superti-Furga,
  • Toshio Hirano

DOI
https://doi.org/10.1371/journal.pone.0003642
Journal volume & issue
Vol. 3, no. 11
p. e3642

Abstract

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BackgroundZinc (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 findingsHere 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/significanceHence, 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.