NDLI: Protection against vascular leak in neprilysin transgenic mice with complex overexpression pattern

Content Provider	Springer Nature Link
Author	Wick, Marilee J. Loomis, Zoe L. Harral, Julie W. Le, Mysan Wehling, Carol A. Miller, York E. Dempsey, Edward C.
Copyright Year	2016
Abstract	Neprilysin (NEP) is a cell surface metallopeptidase found in many tissues. Based mostly on pharmacological manipulations, NEP has been thought to protect blood vessels from plasma extravasation. We have suggested that NEP may protect against pulmonary vascular injury. However, these prior studies did not utilize mice which overexpress NEP. The aims of the present investigation were to develop and characterize doubly transgenic (DT) mice that overexpress NEP universally and conditionally, and to investigate the protective effect that overexpressed NEP may have against plasma extravasation in the vasculature. The duodenum, which is often used to assess vascular permeability, and in which the NEP protein was overexpressed in our DT mice two-fold, was selected as our experimental preparation. We found that substance P-induced plasma extravasation was decreased substantially (3.5-fold) in the duodenums of our doxycycline-treated DT mice, giving independent evidence of NEP’s protective effects against plasma extravasation. Transgenic lung NEP protein was not stably expressed in the DT mice, so we were not able to test the effect of NEP overexpression in the lung. Although initially overexpressed nearly nine-fold at that site, pulmonary NEP protein overexpression eventually dissipated. Surprisingly, at a time when there was no lung transgenic NEP protein overexpression, lung NEP mRNA expression was still increased 23-fold, indicating that the expression defect probably is not transcriptional. These studies help to characterize our complex transgenic model of NEP overexpression and further demonstrate NEP’s protective effects against plasma extravasation.
Starting Page	773
Ending Page	784
Page Count	12
File Format	PDF
ISSN	09628819
Journal	Transgenic Research
Volume Number	25
Issue Number	6
e-ISSN	15739368
Language	English
Publisher	Springer International Publishing
Publisher Date	2016-07-01
Publisher Place	Cham
Access Restriction	One Nation One Subscription (ONOS)
Subject Keyword	Neprilysin Transgenic mouse Vascular leak Evans blue Duodenum Rosa26 promoter Animal Genetics and Genomics Plant Genetics & Genomics Transgenics Biomedical Engineering/Biotechnology Genetic Engineering Molecular Medicine
Content Type	Text
Resource Type	Article
Subject	Genetics Animal Science and Zoology Biotechnology Agronomy and Crop Science

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