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

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

Author information

1
Department of Pharmacology, Max Planck Institute for Heart and Lung Research, Bad Nauheim, Germany.
2
Scientific Service Group Nuclear Magnetic Resonance Imaging, Max Planck Institute for Heart and Lung Research, Bad Nauheim, Germany.
3
Department of Internal Medicine, Justus-Liebig-University Giessen, Universities of Giessen and Marburg Lung Center (UGMLC), Member of the German Center for Lung Research (DZL), Giessen, Germany.
4
Flow Cytometry Service Facility, Max Planck Institute for Heart and Lung Research, Bad Nauheim, Germany.
5
Department of Cellular and Molecular Pathology, German Cancer Research Center (DKFZ), Heidelberg, Germany.
6
Medical Faculty, J.W. Goethe University Frankfurt, Frankfurt, Germany.

Abstract

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.

PMID:
28806758
PMCID:
PMC5555693
DOI:
10.1371/journal.pone.0183166
[Indexed for MEDLINE]
Free PMC Article

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