Lack of endothelial diaphragms in fenestrae and caveolae of mutant Plvap-deficient mice
Lack of endothelial diaphragms in fenestrae and caveolae of mutant Plvap-deficient mice
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DOI：
10.1007/s00418-012-0987-3
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发表时间：
2012-11-01
影响因子：
2.3
通讯作者：
Tamm, Ernst R.
中科院分区：
文献类型：
--
作者：
Herrnberger, Leonie;Seitz, Roswitha;Tamm, Ernst R.
质膜囊泡相关蛋白（PLVAP，PV-1）特异性表达于内皮细胞，其定位于窗孔、小窝和跨内皮通道的隔膜。为了了解其功能，我们产生了缺乏PLVAP的突变小鼠。在C57 BL/6 N遗传背景中，纯合Plvap缺陷胚胎在出生前死亡，并患有皮下水肿、出血和皮下毛细血管血管壁缺陷。此外，Plvap（-/-）胚胎的心脏显示室间隔缺损和较薄的心室壁。在野生型胚胎中，PLVAP和具有气孔隔膜的小窝存在于皮下毛细血管和内皮细胞的内皮细胞中，而隔膜在Plvap（-/-）同窝仔的小窝中缺失。混合C57 BL/6 N/FVB-N遗传背景的Plvap（-/-）小鼠出生并存活最多4周。外分泌和内分泌胰腺和肾管周膜的captured作为有孔毛细血管的例子进行了更详细的研究。在这些血管床中，Plvap（-/-）小鼠显示窗孔、小窝和跨内皮通道中完全没有隔膜，这些发现与内皮窗孔数量的大幅减少相关。毛细血管表型的变化与出生后生长的显著迟缓和贫血有关。Plvap（-/-）小鼠提供了一种动物模型来阐明内皮窗孔的特定功能作用及其对不同器官中水和溶质通过的贡献。
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.