Harald Carlsen, Kanae Ebihara, Nobuyo H Kuwata, Kazuhisa Kuwata, Gamze Aydemir, Ralph Rühl, Rune Blomhoff
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引用次数: 1
Abstract
Background: Vitamin A is essential for a wide range of life processes throughout embryogenesis to adult life. With the aim of developing an in vivo model to monitor retinoic acid receptor (RAR) transactivation real-time in intact animals, we generated transgenic mice carrying a luciferase (luc) reporter gene under the control of retinoic acid response elements (RAREs) consisting of three copies of a direct repeat with five spacing nucleotides (DR5). Methods: Transgenic mice carrying a RARE dependent luciferase reporter flanked with insulator sequence were generated by pronuclear injection. RARE dependent luciferase activity was detected by in vivo imaging or in tissue extracts following manipulations with RAR/retinoid X receptor (RXR) agonists, RAR antagonists or in vitamin A deficient mice. Results: We found a strong induction of luciferase activity in a time and dose dependent manner by retinoic acid as well as RAR agonists, but not by the RXR agonist (using n=4-6 per group; 94 mice). In addition, luciferase activity was strongly reduced in vitamin A-deficient mice (n=6-9; 30 mice). These observations confirm that luciferase activity was controlled by RAR activation in the RARE-luc mouse. Luciferase activity was detectable in various organs, with high activity especially in brain and testis, indicating strong retinoid signalling in these tissues. Conclusion: The RARE-luc transgenic mice, which enabled real-time in vivo assessment of RAR activation, will be useful in understanding the normal physiology of vitamin A, the role of retinoid signalling in pathologies as well as to evaluate pharmacological ligands for RARs.
期刊介绍:
Since 1930 this journal has provided an important international forum for scientific advances in the study of nutrition and vitamins. Widely read by academicians as well as scientists working in major governmental and corporate laboratories throughout the world, this publication presents work dealing with basic as well as applied topics in the field of micronutrients, macronutrients, and non-nutrients such as secondary plant compounds.
The editorial and advisory boards include many of the leading persons currently working in this area.
The journal is of particular interest to:
- Nutritionists
- Vitaminologists
- Biochemists
- Physicians
- Engineers of human and animal nutrition
- Food scientists