Journal article
Fetal inhibition of inflammation improves disease phenotypes in harlequin ichthyosis
DL Cottle, GMA Ursino, SCI Ip, LK Jones, T Ditommaso, DF Hacking, NE Mangan, NA Mellett, KJ Henley, D Sviridov, CA Nold-Petry, MF Nold, PJ Meikle, BT Kile, IM Smyth
Human Molecular Genetics | OXFORD UNIV PRESS | Published : 2015
DOI: 10.1093/hmg/ddu459
Abstract
Harlequin ichthyosis (HI) is a severe skin disease which leads to neonatal death in ~50% of cases. It is the result of mutations in ABCA12, a protein that transports lipids required to establish the protective skin barrier needed after birth. To better understand the life-threatening newborn HI phenotype, we analysed the developing epidermis for consequences of lipid dysregulation in mouse models. We observed a pro-inflammatory signature which was characterized by chemokine upregulation in embryonic skin which is distinct from that seen in other types of ichthyosis. Inflammation also persisted in grafted HI skin. To examine the contribution of inflammation to disease development, we overexpr..
View full abstractGrants
Awarded by National Health and Medical Research Council (Australia)
Awarded by Independent Research Institutes Infrastructure Support Scheme Grant
Awarded by National Health and Medical Research Council
Awarded by Australian Research Council Future Fellowship
Awarded by Australian Research Council
Funding Acknowledgements
This work was supported by the National Health and Medical Research Council (Australia) by a Project grant (1020281 to IS., 1012353 and 1043845 to M.F.N. and C.A.N.P.), Program Grants (461219, 1016647), an Independent Research Institutes Infrastructure Support Scheme Grant (361646), the Victorian Government's Operational Infrastructure Support Program to N.E.M., M.F.N. and C.A.N.P. This work was additionally supported by the following fellowships: an Australian Post-graduate Award to SCII, a Monash International Post-graduate Research Scholarship and Monash Graduate Scholarship to T.D.T., an Australian Research Council Australian Research Fellowship to N.E.M., a Fellowship from the Sylvia and Charles Viertel Foundation to B.T.K., Monash University's Larkins Fellowship to M.F.N., a National Health and Medical Research Council R. Douglas Wright fellowship (384457) an Australian Research Council Future Fellowship (FT100100620) and a Monash University Fellowship to I.S.