Keywords: MMP14, rare bone disease, acne

“Skin and Bones; Studying the effects of MMP14 mutations”

Winchester syndrome (WS) is a rare genetic disease characterised by bone abnormalities, mitral valve insufficiency and acne. WS is caused by mutations in the MMP14 gene. This dissertation shows that a newly-discovered mutation in this gene causes mild WS. The underlying mechanism is the function of the MMP14 protein partly being limited by this mutation. In addition, the importance of MMP14 for tissue remodelling is shown. If abnormal, this causes bone abnormalities and acne. Finally, a new zebrafish model for WS is generated which can be used to develop new treatment options for this disease.