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Conditional mouse models support the role of SLC39A14 (ZIP14) in Hyperostosis Cranialis Interna and in bone homeostasis

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Conditional mouse models support the role of SLC39A14 (ZIP14) in Hyperostosis Cranialis Interna and in bone homeostasis. / Hendrickx, Gretl; Borra, Vere M; Steenackers, Ellen; Yorgan, Timur A; Hermans, Christophe; Boudin, Eveline; Waterval, Jérôme J; Jansen, Ineke D C; Aydemir, Tolunay Beker; Kamerling, Niels; Behets, Geert J; Plumeyer, Christine; D'Haese, Patrick C; Busse, Björn; Everts, Vincent; Lammens, Martin; Mortier, Geert; Cousins, Robert J; Schinke, Thorsten; Stokroos, Robert J; Manni, Johannes J; Van Hul, Wim.

In: PLOS GENET, Vol. 14, No. 4, 04.2018, p. e1007321.

Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review

Harvard

Hendrickx, G, Borra, VM, Steenackers, E, Yorgan, TA, Hermans, C, Boudin, E, Waterval, JJ, Jansen, IDC, Aydemir, TB, Kamerling, N, Behets, GJ, Plumeyer, C, D'Haese, PC, Busse, B, Everts, V, Lammens, M, Mortier, G, Cousins, RJ, Schinke, T, Stokroos, RJ, Manni, JJ & Van Hul, W 2018, 'Conditional mouse models support the role of SLC39A14 (ZIP14) in Hyperostosis Cranialis Interna and in bone homeostasis', PLOS GENET, vol. 14, no. 4, pp. e1007321. https://doi.org/10.1371/journal.pgen.1007321

APA

Hendrickx, G., Borra, V. M., Steenackers, E., Yorgan, T. A., Hermans, C., Boudin, E., Waterval, J. J., Jansen, I. D. C., Aydemir, T. B., Kamerling, N., Behets, G. J., Plumeyer, C., D'Haese, P. C., Busse, B., Everts, V., Lammens, M., Mortier, G., Cousins, R. J., Schinke, T., ... Van Hul, W. (2018). Conditional mouse models support the role of SLC39A14 (ZIP14) in Hyperostosis Cranialis Interna and in bone homeostasis. PLOS GENET, 14(4), e1007321. https://doi.org/10.1371/journal.pgen.1007321

Vancouver

Hendrickx G, Borra VM, Steenackers E, Yorgan TA, Hermans C, Boudin E et al. Conditional mouse models support the role of SLC39A14 (ZIP14) in Hyperostosis Cranialis Interna and in bone homeostasis. PLOS GENET. 2018 Apr;14(4):e1007321. https://doi.org/10.1371/journal.pgen.1007321

Bibtex

@article{79f9e95b74684628a8e761ca6e0695cf,
title = "Conditional mouse models support the role of SLC39A14 (ZIP14) in Hyperostosis Cranialis Interna and in bone homeostasis",
abstract = "Hyperostosis Cranialis Interna (HCI) is a rare bone disorder characterized by progressive intracranial bone overgrowth at the skull. Here we identified by whole-exome sequencing a dominant mutation (L441R) in SLC39A14 (ZIP14). We show that L441R ZIP14 is no longer trafficked towards the plasma membrane and excessively accumulates intracellular zinc, resulting in hyper-activation of cAMP-CREB and NFAT signaling. Conditional knock-in mice overexpressing L438R Zip14 in osteoblasts have a severe skeletal phenotype marked by a drastic increase in cortical thickness due to an enhanced endosteal bone formation, resembling the underlying pathology in HCI patients. Remarkably, L438R Zip14 also generates an osteoporotic trabecular bone phenotype. The effects of osteoblastic overexpression of L438R Zip14 therefore mimic the disparate actions of estrogen on cortical and trabecular bone through osteoblasts. Collectively, we reveal ZIP14 as a novel regulator of bone homeostasis, and that manipulating ZIP14 might be a therapeutic strategy for bone diseases.",
keywords = "Journal Article",
author = "Gretl Hendrickx and Borra, {Vere M} and Ellen Steenackers and Yorgan, {Timur A} and Christophe Hermans and Eveline Boudin and Waterval, {J{\'e}r{\^o}me J} and Jansen, {Ineke D C} and Aydemir, {Tolunay Beker} and Niels Kamerling and Behets, {Geert J} and Christine Plumeyer and D'Haese, {Patrick C} and Bj{\"o}rn Busse and Vincent Everts and Martin Lammens and Geert Mortier and Cousins, {Robert J} and Thorsten Schinke and Stokroos, {Robert J} and Manni, {Johannes J} and {Van Hul}, Wim",
year = "2018",
month = apr,
doi = "10.1371/journal.pgen.1007321",
language = "English",
volume = "14",
pages = "e1007321",
journal = "PLOS GENET",
issn = "1553-7404",
publisher = "Public Library of Science",
number = "4",

}

RIS

TY - JOUR

T1 - Conditional mouse models support the role of SLC39A14 (ZIP14) in Hyperostosis Cranialis Interna and in bone homeostasis

AU - Hendrickx, Gretl

AU - Borra, Vere M

AU - Steenackers, Ellen

AU - Yorgan, Timur A

AU - Hermans, Christophe

AU - Boudin, Eveline

AU - Waterval, Jérôme J

AU - Jansen, Ineke D C

AU - Aydemir, Tolunay Beker

AU - Kamerling, Niels

AU - Behets, Geert J

AU - Plumeyer, Christine

AU - D'Haese, Patrick C

AU - Busse, Björn

AU - Everts, Vincent

AU - Lammens, Martin

AU - Mortier, Geert

AU - Cousins, Robert J

AU - Schinke, Thorsten

AU - Stokroos, Robert J

AU - Manni, Johannes J

AU - Van Hul, Wim

PY - 2018/4

Y1 - 2018/4

N2 - Hyperostosis Cranialis Interna (HCI) is a rare bone disorder characterized by progressive intracranial bone overgrowth at the skull. Here we identified by whole-exome sequencing a dominant mutation (L441R) in SLC39A14 (ZIP14). We show that L441R ZIP14 is no longer trafficked towards the plasma membrane and excessively accumulates intracellular zinc, resulting in hyper-activation of cAMP-CREB and NFAT signaling. Conditional knock-in mice overexpressing L438R Zip14 in osteoblasts have a severe skeletal phenotype marked by a drastic increase in cortical thickness due to an enhanced endosteal bone formation, resembling the underlying pathology in HCI patients. Remarkably, L438R Zip14 also generates an osteoporotic trabecular bone phenotype. The effects of osteoblastic overexpression of L438R Zip14 therefore mimic the disparate actions of estrogen on cortical and trabecular bone through osteoblasts. Collectively, we reveal ZIP14 as a novel regulator of bone homeostasis, and that manipulating ZIP14 might be a therapeutic strategy for bone diseases.

AB - Hyperostosis Cranialis Interna (HCI) is a rare bone disorder characterized by progressive intracranial bone overgrowth at the skull. Here we identified by whole-exome sequencing a dominant mutation (L441R) in SLC39A14 (ZIP14). We show that L441R ZIP14 is no longer trafficked towards the plasma membrane and excessively accumulates intracellular zinc, resulting in hyper-activation of cAMP-CREB and NFAT signaling. Conditional knock-in mice overexpressing L438R Zip14 in osteoblasts have a severe skeletal phenotype marked by a drastic increase in cortical thickness due to an enhanced endosteal bone formation, resembling the underlying pathology in HCI patients. Remarkably, L438R Zip14 also generates an osteoporotic trabecular bone phenotype. The effects of osteoblastic overexpression of L438R Zip14 therefore mimic the disparate actions of estrogen on cortical and trabecular bone through osteoblasts. Collectively, we reveal ZIP14 as a novel regulator of bone homeostasis, and that manipulating ZIP14 might be a therapeutic strategy for bone diseases.

KW - Journal Article

U2 - 10.1371/journal.pgen.1007321

DO - 10.1371/journal.pgen.1007321

M3 - SCORING: Journal article

C2 - 29621230

VL - 14

SP - e1007321

JO - PLOS GENET

JF - PLOS GENET

SN - 1553-7404

IS - 4

ER -