Perinatal lethality and endothelial cell abnormalities in several vessel compartments of fibulin-1-deficient mice
Perinatal lethality and endothelial cell abnormalities in several vessel compartments of fibulin-1-deficient mice
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DOI：
10.1128/mcb.21.20.7025-7034.2001
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发表时间：
2001-10-01
影响因子：
5.3
通讯作者：
Chu, ML
中科院分区：
文献类型：
--
作者：
Kostka, G;Giltay, R;Chu, ML
细胞外基质蛋白纤维蛋白-1是血管壁的独特成分，可以与基底膜、微原纤维和弹性纤维中的其他配体结合。通过小鼠纤维蛋白-1基因的靶向失活，研究了其生物学作用。这导致从妊娠中期开始的几个组织大量出血，最终导致几乎所有纯合子胚胎在出生时死亡。组织学分析显示各种小血管的内皮层扩张和破裂，但在大血管中没有。肾脏表现出明显的肾小球畸形和足细胞紊乱。肺泡发育迟缓提示肺膨胀性损伤。免疫组织学显示在其典型的定位中缺乏纤维蛋白-1，但其他几种细胞外基质蛋白没有异常模式。电镜显示，最严重的器官毛细血管内皮细胞基底膜完整，但细胞质过程不规则。纤维蛋白-1的缺失导致大量失血，但不影响凝血。数据表明，一些内皮细胞间室存在强烈但有限的异常，这可能与一些肾和肺缺陷一起导致早期死亡。
The extracellular matrix protein fibulin-1 is a distinct component of vessel walls and can be associated with other ligands present in basement membranes, microfibrils, and elastic fibers. Its biological role was investigated by the targeted inactivation of the fibulin-1 gene in mice. This led to massive hemorrhages in several tissues starting at midgestation, ultimately resulting in the death of almost all homozygous embryos upon birth. Histological analysis demonstrated dilation and ruptures in the endothelial lining of various small vessels but not in that of larger vessels. Kidneys displayed a distinct malformation of glomeruli and disorganization of podocytes. A delayed development of lung alveoli suggested impairment in lung inflation. Immunohistology demonstrated the absence of fibulin-1 in its typical localizations but no aberrant patterns for several other extracellular matrix proteins. Electron microscopy revealed intact basement membranes but very irregular cytoplasmic processes of capillary endothelial cells in the organs that were most severely affected. Absence of fibulin-1 caused considerable blood loss but did not compromise blood clotting. The data indicate a strong but restricted abnormality in some endothelial compartments which, together with some kidney and lung defects, may be responsible for early death.