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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2021
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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) |
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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 |
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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 |
work_keys_str_mv |
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