{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T05:09:54Z","timestamp":1791263394489,"version":"4.1.0"},"reference-count":25,"publisher":"American Physiological Society","issue":"3","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American Journal of Physiology-Heart and Circulatory Physiology"],"published-print":{"date-parts":[[2014,8,1]]},"abstract":"<jats:p>Covalent modifications such as tyrosine phosphorylation are associated with the breakdown of endothelial cell junctions and increased vascular permeability. We previously showed that vascular endothelial (VE)-cadherin was tyrosine phosphorylated in vivo in the mouse reproductive tract and that Y685 was a target site for Src in response to vascular endothelial growth factor in vitro. In the present study, we aimed to understand the implication of VE-cadherin phosphorylation at site Y685 in cyclic angiogenic organs. To achieve this aim, we generated a knock-in mouse carrying a tyrosine-to-phenylalanine point mutation of VE-cadherin Y685 (VE-Y685F). Although homozygous VE-Y685F mice were viable and fertile, the nulliparous knock-in female mice exhibited enlarged uteri with edema. This phenotype was observed in 30% of females between 4 to 14 mo old. Histological examination of longitudinal sections of the VE-Y685F uterus showed an extensive disorganization of myometrium and endometrium with highly edematous uterine glands, numerous areas with sparse cells, and increased accumulation of collagen fibers around blood vessels, indicating a fibrotic state. Analysis of cross section of ovaries showed the appearance of spontaneous cysts, which suggested increased vascular hyperpermeability. Electron microscopy analysis of capillaries in the ovary showed a slight but significant increase in the gap size between two adjacent endothelial cell membranes in the junctions of VE-Y685F mice (wild-type, 11.5 \u00b1 0.3, n = 78; and VE-Y685F, 12.48 \u00b1 0.3, n = 65; P = 0.045), as well as collagen fiber accumulation around capillaries. Miles assay revealed that either basal or vascular endothelial growth factor-stimulated permeability in the skin was increased in VE-Y685F mice. Since edema and fibrotic appearance have been identified as hallmarks of initial increased vascular permeability, we conclude that the site Y685 in VE-cadherin is involved in the physiological regulation of capillary permeability. Furthermore, this knock-in mouse model is of potential interest for further studies of diseases that are associated with abnormal vascular permeability.<\/jats:p>","DOI":"10.1152\/ajpheart.00774.2013","type":"journal-article","created":{"date-parts":[[2014,5,24]],"date-time":"2014-05-24T05:51:38Z","timestamp":1400910698000},"page":"H455-H463","source":"Crossref","is-referenced-by-count":29,"title":["VE-cadherin Y685F knock-in mouse is sensitive to vascular permeability in recurrent angiogenic organs"],"prefix":"10.1152","volume":"307","author":[{"given":"Adama","family":"Sidib\u00e9","sequence":"first","affiliation":[{"name":"INSERM, U1036, Biology of Cancer and Infection, Grenoble, France;"},{"name":"UJF-Grenoble 1, Biology of Cancer and Infection, Grenoble, France;"},{"name":"CEA, DSV\/iRTSV, Biology of Cancer and Infection, Grenoble, 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