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

被引：223

作者：

Fukada, Toshiyuki ^{[1
,2
]}

Civic, Natacha ^{[3
]}

Furuichi, Tatsuya ^{[4
]}

Shimoda, Shinji ^{[5
]}

Mishima, Kenji ^{[6
]}

Higashiyama, Hiroyuki ^{[6
]}

Idaira, Yayoi ^{[7
]}

Asada, Yoshinobu ^{[7
]}

Kitamura, Hiroshi ^{[8
]}

Yamasaki, Satoru ^{[1
]}

Hojyo, Shintaro ^{[1
,2
]}

Nakayama, Manabu ^{[9
]}

Ohara, Osamu ^{[8
,9
]}

Koseki, Haruhiko ^{[10
]}

dos Santos, Heloisa G. ^{[11
]}

Bonafe, Luisa ^{[12
]}

Ha-Vinh, Russia ^{[12
]}

Zankl, Andreas ^{[12
]}

Unger, Sheila ^{[12
,13
]}

Kraenzlin, Marius E. ^{[14
]}

Beckmann, Jacques S. ^{[3
,15
]}

Saito, Ichiro ^{[6
]}

Rivolta, Carlo ^{[3
]}

Ikegawa, Shiro ^{[4
]}

Superti-Furga, Andrea ^{[12
,13
]}

Hirano, Toshio ^{[1
,16
,17
]}

机构：

[1] RIKEN Res Ctr Allergy & Immunol, Lab Cytokine Signaling, Kanagawa, Japan

[2] Osaka Univ, Grad Sch Med, Dept Allergy & Immunol, Suita, Osaka 565, Japan

[3] Univ Lausanne, Dept Med Genet, CH-1015 Lausanne, Switzerland

[4] RIKEN, Ctr Genom Med, Lab Bone & Joint Dis, Tokyo, Japan

[5] Tsurumi Univ, Sch Dent Med, Dept Anat 1, Kanagawa, Japan

[6] Tsurumi Univ, Sch Dent Med, Dept Pathol, Kanagawa, Japan

[7] Tsurumi Univ, Sch Dent Med, Dept Pediat Dent, Kanagawa, Japan

[8] RIKEN Res Ctr Allergy & Immunol, Lab Immunogenom, Kanagawa, Japan

[9] Kazusa DNA Res Inst, Lab Genome Technol, Chiba, Japan

[10] RIKEN Res Ctr Allergy & Immunol, Lab Dev Genet, Kanagawa, Japan

[11] Hosp S Maria, Serv Genet Med, Lisbon, Portugal

[12] CHU Vaudois, Div Mol Pediat, Lausanne, Switzerland

[13] Univ Freiburg, Dept Paediat & Adolescent Med, D-7800 Freiburg, Germany

[14] Univ Hosp, Div Endocrinol, Diabetes & Clin Nutr, Basel, Switzerland

[15] CHU Vaudois, Serv Med Genet, Lausanne, Switzerland

[16] Osaka Univ, WPI Immunol Frontier Res Ctr, Suita, Osaka 565, Japan

[17] Osaka Univ, Grad Sch Med, Grad Sch Frontier Biosci, CREST Program Japan Sci & Technol Agcy, Suita, Osaka 565, Japan

来源：

PLOS ONE | 2008年 / 3卷 / 11期

关键词：

D O I：

10.1371/journal.pone.0003642

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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.

引用

页数：13

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