Purpose of review: 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.
Recent finding: 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.
Summary: 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.