Developmental vascular remodeling defects and postnatal kidney failure in mice lacking Gpr116 (Adgrf5) and Eltd1 (Adgrl4)

PLoS One. 2017 Aug 14;12(8):e0183166. doi: 10.1371/journal.pone.0183166. eCollection 2017.


GPR116 (ADGRF5) and ELTD1 (ADGRL4) belong to different subfamilies of the adhesion G-protein-coupled receptor group but are both expressed in endothelial cells. We therefore analyzed their functions in mice lacking these receptors. While loss of GPR116 or ELTD1 alone had no obvious effect on cardiovascular or kidney function, mice lacking both, GPR116 and ELTD1, showed malformations of the aortic arch arteries and the cardiac outflow tract leading to perinatal lethality in about 50% of the mutants. In addition to cardiovascular malformations, surviving mice developed renal thrombotic microangiopathy as well as hemolysis and splenomegaly, and their lifespan was significantly reduced. Loss of GPR116 and ELTD1 specifically in endothelial cells or neural crest-derived cells did not recapitulate any of the phenotypes observed in GPR116-ELTD1 double deficient mice, indicating that loss of GPR116 and ELTD1 expressed by other cells accounts for the observed cardiovascular and renal defects.

MeSH terms

  • Animals
  • Animals, Newborn
  • Arteries / abnormalities
  • Arteries / pathology
  • Cardiomegaly / complications
  • Cardiomegaly / metabolism
  • Cardiomegaly / pathology
  • Cardiovascular Abnormalities / complications
  • Cardiovascular Abnormalities / pathology
  • Embryo, Mammalian / metabolism
  • Embryo, Mammalian / pathology
  • Hemolysis
  • Mice, Knockout
  • Receptors, G-Protein-Coupled / deficiency*
  • Receptors, G-Protein-Coupled / metabolism
  • Renal Insufficiency / complications
  • Renal Insufficiency / embryology
  • Renal Insufficiency / pathology
  • Renal Insufficiency / physiopathology*
  • Splenomegaly / complications
  • Splenomegaly / pathology
  • Thrombotic Microangiopathies / complications
  • Thrombotic Microangiopathies / pathology
  • Vascular Remodeling*


  • Gpr116 protein, mouse
  • Receptors, G-Protein-Coupled

Grant support

The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.