PloS one · 2008
The zinc transporter SLC39A13/ZIP13 is required for connective tissue development; its involvement in BMP/TGF-beta signaling pathways.
Клинический случайСтатьяПоддержка исследования: вне правительства СШАНазвание и аннотация: Перевод в очереди
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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
Аннотация
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.
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.
Предметные рубрики MeSH
AdolescentAmino Acid SequenceAnimalsBone Morphogenetic ProteinsCation Transport ProteinsCells, CulturedConnective TissueDNA Mutational AnalysisEhlers-Danlos SyndromeHumansMiceMice, KnockoutModels, BiologicalMolecular Sequence DataMorphogenesisOsteogenesisPedigreeSequence Homology, Amino AcidSignal TransductionTransforming Growth Factor betaYoung AdultZinc