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Development of CIDEA reporter mouse model and its application for screening thermogenic drugs.
Son, Yeonho; Choi, Cheoljun; Song, Cheol; Im, Hyeonyeong; Cho, Yoon Keun; Son, Ju Seung; Joo, Sungug; Joh, Yoonjoe; Lee, Young Jae; Seong, Je Kyung; Lee, Yun-Hee.
Afiliación
  • Son Y; College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University, Seoul, Republic of Korea.
  • Choi C; College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University, Seoul, Republic of Korea.
  • Song C; Korea Mouse Phenotyping Center (KMPC) and Lee Gil Ya Cancer and Diabetes Institute, Gachon University, Inchon, Republic of Korea.
  • Im H; College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University, Seoul, Republic of Korea.
  • Cho YK; College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University, Seoul, Republic of Korea.
  • Son JS; College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University, Seoul, Republic of Korea.
  • Joo S; College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University, Seoul, Republic of Korea.
  • Joh Y; College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University, Seoul, Republic of Korea.
  • Lee YJ; Korea Mouse Phenotyping Center (KMPC) and Lee Gil Ya Cancer and Diabetes Institute, Gachon University, Inchon, Republic of Korea. leeyj@gachon.ac.kr.
  • Seong JK; Department of Biochemistry, College of Medicine, Gachon University, Inchon, Republic of Korea. leeyj@gachon.ac.kr.
  • Lee YH; Korea Mouse Phenotyping Center (KMPC) and Laboratory of Developmental Biology and Genomics, Research Institute for Veterinary Science, and BK 21 PLUS Program for Creative Veterinary Science Research, College of Veterinary Medicine, Seoul National University, Seoul, Republic of Korea. snumouse@snu.ac
Sci Rep ; 11(1): 18429, 2021 09 16.
Article en En | MEDLINE | ID: mdl-34531447
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 ß3-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.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Ingeniería Genética / Termogénesis / Proteínas Reguladoras de la Apoptosis / Descubrimiento de Drogas Tipo de estudio: Diagnostic_studies / Prognostic_studies / Screening_studies Límite: Animals Idioma: En Revista: Sci Rep Año: 2021 Tipo del documento: Article Pais de publicación: Reino Unido
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Ingeniería Genética / Termogénesis / Proteínas Reguladoras de la Apoptosis / Descubrimiento de Drogas Tipo de estudio: Diagnostic_studies / Prognostic_studies / Screening_studies Límite: Animals Idioma: En Revista: Sci Rep Año: 2021 Tipo del documento: Article Pais de publicación: Reino Unido