Projects per year
Abstract
Harlequin ichthyosis (HI) is a severe skin disease which leads to neonatal death in approximately 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 overexpressed interleukin-37b to globally suppress fetal inflammation, observing considerable improvements in keratinocyte differentiation. These studies highlight inflammation as an unexpected contributor to HI disease development in utero, and suggest that inhibiting inflammation may reduce disease severity.
Original language | English |
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Pages (from-to) | 436-449 |
Number of pages | 14 |
Journal | Human Molecular Genetics |
Volume | 24 |
Issue number | 2 |
DOIs | |
Publication status | Published - 2015 |
Projects
- 4 Finished
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ABCA12-A new regulator of cellular lipid metabolism and inflammation
Smyth, I., Kelsell, D. & Fu, Y.
National Health and Medical Research Council (NHMRC) (Australia)
1/01/12 → 31/12/14
Project: Research
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Using mouse genetics to understand skin development and cell biology
Australian Research Council (ARC), Monash University
31/05/11 → 31/05/15
Project: Research
Equipment
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Histology Platform
Camilla Cohen (Manager)
Faculty of Medicine Nursing and Health Sciences Research PlatformsFacility/equipment: Facility
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MHTP Medical Genomics Facility
Trevor Wilson (Manager)
Hudson Institute - Department of Molecular and Translational ScienceFacility/equipment: Facility