Transgenic mouse model for imaging of ATF4 translational activation-related cellular stress responses in vivo
| Autor: | Naoki Takeda, Takao Iwawaki, Tomo O. Ishikawa, Ryoko Akai, Ken Ichi Yamamura, Takae Toyoshima |
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| Jazyk: | angličtina |
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Genetically modified mouse Cellular adaptation Gene Expression Mice Transgenic Activating Transcription Factor 4 Article 03 medical and health sciences Mice 0302 clinical medicine In vivo Genes Reporter Stress Physiological Animals Humans Multidisciplinary Chemistry Endoplasmic reticulum ATF4 Fibroblasts Cell biology Molecular Imaging 030104 developmental biology Protein Biosynthesis Translational Activation 030217 neurology & neurosurgery Ex vivo |
| Zdroj: | Scientific Reports |
| ISSN: | 2045-2322 |
| Popis: | Activating transcription factor 4 (ATF4) is a translationally activated protein that plays a role in cellular adaptation to several stresses. Because these stresses are associated with various diseases, the translational control of ATF4 needs to be evaluated from the physiological and pathological points of view. We have developed a transgenic mouse model to monitor the translational activation of ATF4 in response to cellular stress. By using this mouse model, we were able to detect nutrient starvation response, antivirus response, endoplasmic reticulum (ER) stress response, and oxidative stress in vitro and ex vivo, as well as in vivo. The reporter system introduced into our mouse model was also shown to work in a stress intensity-dependent manner and a stress duration-dependent manner. The mouse model is therefore a useful tool for imaging ATF4 translational activation at various levels, from cell cultures to whole bodies, and it has a range of useful applications in investigations on the physiological and pathological roles of ATF4-related stress and in the development of clinical drugs for treating ATF4-associated diseases. |
| Databáze: | OpenAIRE |
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