eLife Assessment
In this manuscript, the authors describe the creation of a transgenic mouse expressing a reporter for Integrated Stress Response (ISR) activation in a CRE-dependent manner. Reliable tools for detecting ISR activation in situ are lacking, so this manuscript describes a potentially valuable tool that builds on and overcomes some of the limitations of a similar viral vector described by the authors in a previous publication. Solid evidence suggests that distinct populations of cells (ChAT) in the nervous system are marked by some level of ISR activation, and that the mouse could be most helpful as a screen for cell types in which the ISR is particularly active, although it would be difficult to draw conclusions from the reporter alone. Additional validations of the reporter activity in situ will further strengthen the manuscript.