| Autor: |
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. |
| Předmět: |
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| Zdroj: |
PLoS ONE; 2008, Vol. 3 Issue 11, p1-13, 13p, 3 Color Photographs, 1 Diagram, 3 Graphs |
| Abstrakt: |
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. [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
| Externí odkaz: |
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