09 September 2020
Vol 12, Issue 560

About The Cover

Cover image expansion

ONLINE COVER Complex Mutations in Primary Lymphedema. The model shows angiopoietin-2 (ANGPT2) complexed with its receptors TIE1 and TIE2, factors involved in the regulation of vascular integrity. Leppänen et al. found that inactivating mutations in human ANGPT2 associated with primary lymphedema, a condition marked by tissue swelling resulting from impaired lymphatic function. These dominant negative mutations altered oligomerization and reduced ANGPT2 secretion or its interaction with integrin α5 (at sites highlighted in purple) in lymphatic endothelial cells, and one tested mutation resulted in hyperplastic and dilated lymphatic vessels when overexpressed in mouse ear skin. This work adds to the primary genetic factors associated with lymphedema in humans. [CREDIT: LEPPÄNEN ET AL./SCIENCE TRANSLATIONAL MEDICINE]