Development of CIDEA reporter mouse model and its application for screening thermogenic drugs

Abstract Cell death-inducing DNA fragmentation factor-like effector A (CIDEA) is a lipid droplet-associated protein and is a known marker of the thermogenic capacity of brown/beige adipocytes. To monitor the expression of CIDEA in live mice in a non-invasive manner, we generated CIDEA reporter mice...

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Autores principales: Yeonho Son, Cheoljun Choi, Cheol Song, Hyeonyeong Im, Yoon Keun Cho, Ju Seung Son, Sungug Joo, Yoonjoe Joh, Young Jae Lee, Je Kyung Seong, Yun-Hee Lee
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Publicado: Nature Portfolio 2021
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Acceso en línea:https://doaj.org/article/b8ad4613a74f4a8b8b944e3624538d61
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spelling oai:doaj.org-article:b8ad4613a74f4a8b8b944e3624538d612021-12-02T18:02:30ZDevelopment of CIDEA reporter mouse model and its application for screening thermogenic drugs10.1038/s41598-021-97959-02045-2322https://doaj.org/article/b8ad4613a74f4a8b8b944e3624538d612021-09-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-97959-0https://doaj.org/toc/2045-2322Abstract Cell death-inducing DNA fragmentation factor-like effector A (CIDEA) is a lipid droplet-associated protein and is a known marker of the thermogenic capacity of brown/beige adipocytes. To monitor the expression of CIDEA in live mice in a non-invasive manner, we generated CIDEA reporter mice expressing multicistronic mRNAs encoding CIDEA, luciferase 2, and tdTomato proteins under the control of the Cidea promoter. The expression level of endogenous CIDEA protein in adipose tissue was not affected by the expression of polycistronic reporters. The two CIDEA reporters, luciferase 2 and tdTomato, correctly reflected CIDEA protein levels. Importantly, luciferase activity was induced by cold exposure and the treatment with β3-adrenergic receptor agonist CL316,243 in interscapular and inguinal adipose tissue, which was detectable by in vivo bioluminescence imaging. We further evaluated the effects of candidate brown adipogenic agents using this CIDEA reporter system and demonstrated a positive correlation between drug-induced luciferase activity and thermogenic gene expression levels both in vitro and in vivo. Collectively, we established a dual CIDEA reporter mouse model in which fluorescence and luminescence signals correctly reflect CIDEA expression, and therefore, suggested that this reporter system can be used to evaluate the thermogenic efficacy of candidate molecules.Yeonho SonCheoljun ChoiCheol SongHyeonyeong ImYoon Keun ChoJu Seung SonSungug JooYoonjoe JohYoung Jae LeeJe Kyung SeongYun-Hee LeeNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-13 (2021)
institution DOAJ
collection DOAJ
language EN
topic Medicine
R
Science
Q
spellingShingle Medicine
R
Science
Q
Yeonho Son
Cheoljun Choi
Cheol Song
Hyeonyeong Im
Yoon Keun Cho
Ju Seung Son
Sungug Joo
Yoonjoe Joh
Young Jae Lee
Je Kyung Seong
Yun-Hee Lee
Development of CIDEA reporter mouse model and its application for screening thermogenic drugs
description Abstract Cell death-inducing DNA fragmentation factor-like effector A (CIDEA) is a lipid droplet-associated protein and is a known marker of the thermogenic capacity of brown/beige adipocytes. To monitor the expression of CIDEA in live mice in a non-invasive manner, we generated CIDEA reporter mice expressing multicistronic mRNAs encoding CIDEA, luciferase 2, and tdTomato proteins under the control of the Cidea promoter. The expression level of endogenous CIDEA protein in adipose tissue was not affected by the expression of polycistronic reporters. The two CIDEA reporters, luciferase 2 and tdTomato, correctly reflected CIDEA protein levels. Importantly, luciferase activity was induced by cold exposure and the treatment with β3-adrenergic receptor agonist CL316,243 in interscapular and inguinal adipose tissue, which was detectable by in vivo bioluminescence imaging. We further evaluated the effects of candidate brown adipogenic agents using this CIDEA reporter system and demonstrated a positive correlation between drug-induced luciferase activity and thermogenic gene expression levels both in vitro and in vivo. Collectively, we established a dual CIDEA reporter mouse model in which fluorescence and luminescence signals correctly reflect CIDEA expression, and therefore, suggested that this reporter system can be used to evaluate the thermogenic efficacy of candidate molecules.
format article
author Yeonho Son
Cheoljun Choi
Cheol Song
Hyeonyeong Im
Yoon Keun Cho
Ju Seung Son
Sungug Joo
Yoonjoe Joh
Young Jae Lee
Je Kyung Seong
Yun-Hee Lee
author_facet Yeonho Son
Cheoljun Choi
Cheol Song
Hyeonyeong Im
Yoon Keun Cho
Ju Seung Son
Sungug Joo
Yoonjoe Joh
Young Jae Lee
Je Kyung Seong
Yun-Hee Lee
author_sort Yeonho Son
title Development of CIDEA reporter mouse model and its application for screening thermogenic drugs
title_short Development of CIDEA reporter mouse model and its application for screening thermogenic drugs
title_full Development of CIDEA reporter mouse model and its application for screening thermogenic drugs
title_fullStr Development of CIDEA reporter mouse model and its application for screening thermogenic drugs
title_full_unstemmed Development of CIDEA reporter mouse model and its application for screening thermogenic drugs
title_sort development of cidea reporter mouse model and its application for screening thermogenic drugs
publisher Nature Portfolio
publishDate 2021
url https://doaj.org/article/b8ad4613a74f4a8b8b944e3624538d61
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