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Epithelial overexpression of human ACE2 in mice as a model for studying renal disease
Journal of the American Society of Nephrology ; 32:831, 2021.
Article in English | EMBASE | ID: covidwho-1489565
ABSTRACT

Background:

ACE2 is an integral part of the renin angiotensin system (RAS) and is highly expressed at the brush border of epithelial cells of the renal proximal tubule. Within the lumen, ACE2 is poised to metabolize angiotensin II and extinguish its effects as part of the counter-regulatory arm of the RAS. Use of transgenic mouse models has been essential in exploring the cardiovascular and renal functions of ACE2. Limitations in using mouse models for SARS was overcome by generation of mice expressing human ACE2 (hACE2) downstream of the keratin 18 promoter (K18-hACE2) by McCray et al 2007. K18-hACE2 mice express hACE2 in epithelial cells throughout the body and have proved valuable for the study of SARS-CoV and CoV2 viral infectivity and pathogenesis. Here, we investigate whether K18-hACE2 mice might serve as a unique tool with which to study the role of ACE2 in the intra-renal RAS.

Methods:

We assessed ACE2 activity in urine collected from K18-hACE2 mice (obtained from Jax and bred in our own colony) and their wildtype littermates. Urine was collected over 24 hours in individual metabolic cages, and enzymatic activity was determined using an ACE2 activity assay. Duplicate samples tested for each animal.

Results:

Our lab has a longstanding interest in the role of ACE2 in the kidney and our preliminary experiments demonstrate that K18-hACE2 mice have significantly increased ACE2 enzymatic activity in the urine compared to wildtype littermates (1597.0±379.74 vs 396.0±143.92, p=0.013).

Conclusions:

The increased urinary ACE2 activity suggests that there are elevated levels of ACE2 reaching the kidney. While this seems most likely due to increased expression of renal epithelial ACE2, soluble ACE2 derived elsewhere and able to reach the lumen of the nephron must also be considered. Thus, K18-hACE2 mice with increased urinary ACE2 activity can serve as a model to examine the effect of ACE2 and the RAS on kidney diseases such as hypertension and acute renal injury.
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Collection: Databases of international organizations Database: EMBASE Language: English Journal: Journal of the American Society of Nephrology Year: 2021 Document Type: Article

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Collection: Databases of international organizations Database: EMBASE Language: English Journal: Journal of the American Society of Nephrology Year: 2021 Document Type: Article