| WANG, Y., X. ZHOU, K. OBEROI, R. PHELPS, R. COUWENHOVEN, M. SUN, A. REZZA, G. HOLMES, Ch.J. PERCIVAL, J. FRIEDENTHAL, Pavel KREJČÍ, J.T. RICHTSMEIER, D.L. HUSO, Michael RENDL and E. WANG JABS. p38 Inhibition ameliorates skin and skull abnormalities in Fgfr2 Beare-Stevenson mice. The journal of clinical investigation. [New York, N.Y.]: American Society for Clinical Investigation, 2012, vol. 122, No 6, p. 2153-2164. ISSN 0021-9738. Available from: https://dx.doi.org/10.1172/JCI62644. |
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@article{982600,
author = {Wang, Y. and Zhou, X. and Oberoi, K. and Phelps, R. and Couwenhoven, R. and Sun, M. and Rezza, A. and Holmes, G. and Percival, Ch.J. and Friedenthal, J. and Krejčí, Pavel and Richtsmeier, J.T. and Huso, D.L. and Rendl, Michael and Wang Jabs, E.},
article_location = {[New York, N.Y.]},
article_number = {6},
doi = {http://dx.doi.org/10.1172/JCI62644},
keywords = {p38; skin; skull; FGFR2; Beare-Stevenson syndrome},
language = {eng},
issn = {0021-9738},
journal = {The journal of clinical investigation},
title = {p38 Inhibition ameliorates skin and skull abnormalities in Fgfr2 Beare-Stevenson mice.},
volume = {122},
year = {2012}
}
TY - JOUR
ID - 982600
AU - Wang, Y. - Zhou, X. - Oberoi, K. - Phelps, R. - Couwenhoven, R. - Sun, M. - Rezza, A. - Holmes, G. - Percival, Ch.J. - Friedenthal, J. - Krejčí, Pavel - Richtsmeier, J.T. - Huso, D.L. - Rendl, Michael - Wang Jabs, E.
PY - 2012
TI - p38 Inhibition ameliorates skin and skull abnormalities in Fgfr2 Beare-Stevenson mice.
JF - The journal of clinical investigation
VL - 122
IS - 6
SP - 2153-2164
EP - 2153-2164
PB - American Society for Clinical Investigation
SN - 00219738
KW - p38
KW - skin
KW - skull
KW - FGFR2
KW - Beare-Stevenson syndrome
N2 - Beare-Stevenson cutis gyrata syndrome (BSS) is a human genetic disorder characterized by skin and skull abnormalities. BSS is caused by mutations in the FGF receptor 2 (FGFR2), but the molecular mechanisms that induce skin and skull abnormalities are unclear. We developed a mouse model of BSS harboring a FGFR2 Y394C mutation and identified p38 MAPK as an important signaling pathway mediating these abnormalities. Fgfr2+/Y394C mice exhibited epidermal hyperplasia and premature closure of cranial sutures (craniosynostosis) due to abnormal cell proliferation and differentiation. We found ligand-independent phosphorylation of FGFR2 and activation of p38 signaling in mutant skin and calvarial tissues. Treating Fgfr2+/Y394C mice with a p38 kinase inhibitor attenuated skin abnormalities by reversing cell proliferation and differentiation to near normal levels. This study reveals the pleiotropic effects of the FGFR2 Y394C mutation evidenced by cutis gyrata, acanthosis nigricans, and craniosynostosis and provides a useful model for investigating the molecular mechanisms of skin and skull development. The demonstration of a pathogenic role for p38 activation may lead to the development of therapeutic strategies for BSS and related conditions, such as acanthosis nigricans or craniosynostosis.
ER -
WANG, Y., X. ZHOU, K. OBEROI, R. PHELPS, R. COUWENHOVEN, M. SUN, A. REZZA, G. HOLMES, Ch.J. PERCIVAL, J. FRIEDENTHAL, Pavel KREJČÍ, J.T. RICHTSMEIER, D.L. HUSO, Michael RENDL and E. WANG JABS. p38 Inhibition ameliorates skin and skull abnormalities in Fgfr2 Beare-Stevenson mice. \textit{The journal of clinical investigation}. [New York, N.Y.]: American Society for Clinical Investigation, 2012, vol.~122, No~6, p.~2153-2164. ISSN~0021-9738. Available from: https://dx.doi.org/10.1172/JCI62644.
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