title: The CCAAT/enhancer-binding protein-ATF response elements-luciferase mouse model, an innovative tool to monitor the integrated stress response pathway in vivo.
abstract: OBJECTIVE
  The article highlights the recent development of an ATF4 (activating transcription factor) inducible luciferase (LUC) mouse model to monitor the integrated stress response pathway (ISR) in vivo.
  
  
  RESULTS
  The ISR pathway plays a key role in cellular adaptation to stress and is dysregulated in numerous diseases. The core event in this pathway is the phosphorylation of eukaryotic translation initiation factor 2 α, which leads to the recruitment of the transcription factor ATF4 to specific CCAAT/enhancer-binding protein-ATF response elements (CAREs) located in the promoters of target genes. To monitor the modulation of this pathway in the whole animal and at tissue and cellular levels, we generated a CARE-driven LUC mouse model. We validated the relevance of this model to study stress-related pathologies and recently observed the correlation between the ISR pathway induction in muscle and the occurrence of stress-induced skeletal muscle atrophy.
  
  
  CONCLUSIONS
  The CARE-LUC mouse model represents an innovative tool for investigating the role of the ISR pathway in physiology and disease and opens new avenues for the development of drugs that could modify this important pathway in stress-related human diseases.
authors.affiliation: Université Clermont Auvergne, INRA, UMR1019, UNH, Unité de Nutrition Humaine, CRNH Auvergne, F-63000 Clermont-Ferrand, France.
authors.forename: Alain
authors.initials: A
authors.lastname: Bruhat
authors.forename: Pierre
authors.initials: P
authors.lastname: Fafournoux
mesh_terms: D051701:Activating Transcription Factor 4 / Q000502:physiology*; D000818:Animals; D008156:Luciferases / Q000502:physiology*; D051379:Mice; D023421:Models, Animal; D018482:Muscle, Skeletal / Q000378:metabolism; D009133:Muscular Atrophy / Q000503:physiopathology; D010766:Phosphorylation / Q000502:physiology; D011401:Promoter Regions, Genetic / Q000502:physiology; D017346:Protein Serine-Threonine Kinases; D015398:Signal Transduction / Q000502:physiology*; D013312:Stress, Physiological / Q000502:physiology*
chemical_list: C081452:Atf4 protein, mouse; D051701:Activating Transcription Factor 4; D008156:Luciferases; C070634:Eif2ak4 protein, mouse; D017346:Protein Serine-Threonine Kinases