title: Transgenic mouse model for imaging of ATF4 translational activation-related cellular stress responses in vivo.
abstract: 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.
authors.affiliation: Division of Cell Medicine, Department of Life Science, Medical Research Institute, Kanazawa Medical University, 1-1 Daigaku, Uchinada, Kahoku, Ishikawa 920-0293, Japan.|Iwawaki laboratory, Education and Research Support Center, Graduate School of Medicine, Gunma University, 3-39-22 Showa-machi, Maebashi, Gunma 371-8511, Japan.
authors.forename: Takao
authors.initials: T
authors.lastname: Iwawaki
authors.affiliation: Division of Cell Medicine, Department of Life Science, Medical Research Institute, Kanazawa Medical University, 1-1 Daigaku, Uchinada, Kahoku, Ishikawa 920-0293, Japan.|Iwawaki laboratory, Education and Research Support Center, Graduate School of Medicine, Gunma University, 3-39-22 Showa-machi, Maebashi, Gunma 371-8511, Japan.
authors.forename: Ryoko
authors.initials: R
authors.lastname: Akai
authors.affiliation: Iwawaki laboratory, Education and Research Support Center, Graduate School of Medicine, Gunma University, 3-39-22 Showa-machi, Maebashi, Gunma 371-8511, Japan.
authors.forename: Takae
authors.initials: T
authors.lastname: Toyoshima
authors.affiliation: Division of Developmental Genetics, Institute of Resource Development and Analysis, Kumamoto University, 2-2-1 Honjo, Kumamoto 860-0811, Japan.
authors.forename: Naoki
authors.initials: N
authors.lastname: Takeda
authors.affiliation: TransGenic Inc, 7-1-14 Minatojima-minamimachi, Chuo-ku, Kobe, Hyogo 650-0047, Japan.
authors.forename: Tomo-O
authors.initials: TO
authors.lastname: Ishikawa
authors.affiliation: TransGenic Inc, 7-1-14 Minatojima-minamimachi, Chuo-ku, Kobe, Hyogo 650-0047, Japan.|Yamamura Project Laboratory, Institute of Resource Development and Analysis, Kumamoto University, 2-2-1 Honjo, Chuoku, Kumamoto 860-0811, Japan.
authors.forename: Ken-Ichi
authors.initials: KI
authors.lastname: Yamamura
mesh_terms: D051701:Activating Transcription Factor 4 / Q000378:metabolism; D000818:Animals; D005347:Fibroblasts; D015870:Gene Expression; D017930:Genes, Reporter; D006801:Humans; D051379:Mice; D008822:Mice, Transgenic; D057054:Molecular Imaging; D014176:Protein Biosynthesis; D013312:Stress, Physiological
chemical_list: D051701:Activating Transcription Factor 4