p38 Inhibition ameliorates skin and skull abnormalities in Fgfr2 Beare-Stevenson mice.

Investor logo
Investor logo

Warning

This publication doesn't include Faculty of Sports Studies. It includes Faculty of Science. Official publication website can be found on muni.cz.
Authors

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.

Year of publication 2012
Type Article in Periodical
Magazine / Source The journal of clinical investigation
MU Faculty or unit

Faculty of Science

Citation
Doi http://dx.doi.org/10.1172/JCI62644
Field Physiology
Keywords p38; skin; skull; FGFR2; Beare-Stevenson syndrome
Description 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.
Related projects:

You are running an old browser version. We recommend updating your browser to its latest version.

More info