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

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

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish
Article number18429
JournalScientific reports
Volume11
Issue number1
DOIs
Publication statusPublished - 2021 Dec

Bibliographical note

Funding Information:
We thank Dr. Jin-Hyun Jeong for providing PMSF compounds. We thank Jinyoung Kim for his technical assistance with confocal microscopy. This research was supported by the National Research Foundation of Korea (NRF) Grants (NRF-2019R1C1C1002014, NRF-2018R1A5A2024425, NRF-2014M3A9D5A01075128, NRF-2013M3A9D5072550) funded by the Korean government (the Ministry of Science and ICT).

Publisher Copyright:
© 2021, The Author(s).

All Science Journal Classification (ASJC) codes

  • General

Fingerprint

Dive into the research topics of 'Development of CIDEA reporter mouse model and its application for screening thermogenic drugs'. Together they form a unique fingerprint.

Cite this