The Zinc Transporter SLC39A13/ZIP13 Is Required for Connective Tissue Development; Its Involvement in BMP/TGF-β Signaling Pathways

Fukada, Toshiyuki, Civic, Natacha, Furuichi, Tatsuya, Shimoda, Shinji, Mishima, Kenji, Higashiyama, Hiroyuki, Idaira, Yayoi, Asada, Yoshinobu, Kitamura, Hiroshi, Yamasaki, Satoru, Hojyo, Shintaro, Nakayama, Manabu, Ohara, Osamu, Koseki, Haruhiko, dos Santos, Heloisa G., Bonafe, Luisa, Ha-Vinh, Russia, Zankl, Andreas, Unger, Sheila, Kraenzlin, Marius E., Beckmann, Jacques S., Saito, Ichiro, Rivolta, Carlo, Ikegawa, Shiro, Superti-Furga, Andrea and Hirano, Toshio (2008) The Zinc Transporter SLC39A13/ZIP13 Is Required for Connective Tissue Development; Its Involvement in BMP/TGF-β Signaling Pathways. PloS One, 3 11: e3642.1-e3642.13. doi:10.1371/journal.pone.0003642


Author Fukada, Toshiyuki
Civic, Natacha
Furuichi, Tatsuya
Shimoda, Shinji
Mishima, Kenji
Higashiyama, Hiroyuki
Idaira, Yayoi
Asada, Yoshinobu
Kitamura, Hiroshi
Yamasaki, Satoru
Hojyo, Shintaro
Nakayama, Manabu
Ohara, Osamu
Koseki, Haruhiko
dos Santos, Heloisa G.
Bonafe, Luisa
Ha-Vinh, Russia
Zankl, Andreas
Unger, Sheila
Kraenzlin, Marius E.
Beckmann, Jacques S.
Saito, Ichiro
Rivolta, Carlo
Ikegawa, Shiro
Superti-Furga, Andrea
Hirano, Toshio
Title The Zinc Transporter SLC39A13/ZIP13 Is Required for Connective Tissue Development; Its Involvement in BMP/TGF-β Signaling Pathways
Journal name PloS One   Check publisher's open access policy
ISSN 1932-6203
Publication date 2008-11
Sub-type Article (original research)
DOI 10.1371/journal.pone.0003642
Open Access Status DOI
Volume 3
Issue 11
Start page e3642.1
End page e3642.13
Total pages 13
Place of publication San Francisco, CA, United States
Publisher Public Library of Science
Language eng
Subject 1103 Clinical Sciences
Formatted 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.

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-β 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-β signaling pathways. The Slc39a13-KO mouse represents a novel animal model linking zinc metabolism, BMP/TGF-β signaling and connective tissue dysfunction.
Keyword Zinc
essential trace element
Connective Tissues
biological roles
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status Non-UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Excellence in Research Australia (ERA) - Collection
UQ Centre for Clinical Research Publications
 
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Created: Wed, 13 Jan 2010, 10:31:48 EST by Maria Campbell on behalf of Faculty Of Health Sciences