Limitations of the GENSAT Egr1-EGFP transgenic mouse strain for neural circuit activity mapping

Transgenic immediate-early gene reporter mouse strains are valuable tools for studying activity-dependent neural cell populations in vivo. However, routine characterization of the Gene Expression Nervous System Atlas (GENSAT) Egr1-EGFP reporter mouse strain produced results that were highly inconsistent with endogenous Egr1 expression. Activity-dependent EGFP expression was not observed, and EGFP protein did not co-localize with native Egr1 protein. This precautionary study outlines the limitations of the Egr1-EGFP transgenic line as a tool to study the activity-dependent expression of Egr1 and emphasizes the necessity of taking into account the potential loss of regulatory elements, stability determinants, or translational modulation in transgenic reporter strains.