Lack of endothelial diaphragms in fenestrae and caveolae of mutant Plvap-deficient mice.
Plasmalemmal vesicle-associated protein (PLVAP, PV-1) is specifically expressed in endothelial cells in which it localizes to diaphragms of fenestrae, caveolae, and transendothelial channels. To learn about its function, we generated mutant mice that lack PLVAP. In a C57BL/6N genetic background, homozygous Plvap-deficient embryos die before birth and suffer from subcutaneous edema, hemorrhages, and defects in the vascular wall of subcutaneous capillaries. In addition, hearts of Plvap(-/-) embryos show ventricular septal defects and thinner ventricular walls. In wild-type embryos, PLVAP and caveolae with a stomatal diaphragm are present in endothelial cells of subcutaneous capillaries and endocardium, while a diaphragm is missing in caveolae of Plvap(-/-) littermates. Plvap(-/-) mice in a mixed C57BL/6N/FVB-N genetic background are born and survive at the most for 4 weeks. Capillaries of exocrine and endocrine pancreas and of kidney peritubular interstitium were investigated in more detail as examples of fenestrated capillaries. In these vascular beds, Plvap(-/-) mice show a complete absence of diaphragms in fenestrae, caveolae, and transendothelial channels, findings which are associated with a substantial decrease in the number of endothelial fenestrae. The changes in the capillary phenotype correlate with a considerable retardation of postnatal growth and anemia. Plvap(-/-) mice provide an animal model to clarify the specific functional role of endothelial fenestrae and their contribution to passage of water and solutes in different organs.
Institute of Human Anatomy and Embryology, University of Regensburg, Universitätsstr. 31, 93053, Regensburg, Germany.
Leonie
L
Herrnberger
Roswitha
R
Seitz
Sabrina
S
Kuespert
Michael R
MR
Bösl
Rudolf
R
Fuchshofer
Ernst R
ER
Tamm
D000818:Animals; D002196:Capillaries / Q000002:abnormalities; D002352:Carrier Proteins / Q000235:genetics*; D021941:Caveolae; D004699:Endocardium / Q000002:abnormalities; D004730:Endothelium, Vascular / Q000002:abnormalities*; D005260:Female; D006720:Homozygote; D007668:Kidney / Q000002:abnormalities / Q000098:blood supply; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D051379:Mice; D008810:Mice, Inbred C57BL; D023421:Models, Animal; D009154:Mutation; D010179:Pancreas / Q000002:abnormalities / Q000098:blood supply
D002352:Carrier Proteins; D008565:Membrane Proteins; C486772:Plvap protein, mouse