Fluorescent protein transgenic mice for the study of Ca²⁺ and redox signaling

Many unanswered questions of physiology and medicine require in vivo studies of cellular processes in murine models. These processes commonly depend on intracellular Ca²⁺ and redox alterations. Fluorescent dyes have succeeded in real-time intracellular monitoring of Ca²⁺, redox and the different Reactive Oxygen Species (ROS) in single cells, but have seldomly been applied in vivo. The advance in Fluorescent Protein (FP) technology has created alternative tools for the same task, which can be delivered with viruses or genomic integration strategies into mice. With the availability of several color options for both Ca²⁺ and redox reporting FP, multiparameter measurements have also become feasible: measuring different species, and the same parameter at different locations using organelle-specific targeting sequences at the same time. We, here, focus on mice with genomic integration of Ca²⁺ and redox reporters, provide a list of the available models and summarize the strategies of their generation and utilization. We also describe a novel Calcium DoubleSpy mouse model that conditionally expresses both RCaMP in the cytoplasm and GEM-GECO1 in the mitochondrial matrix, allowing the study of mitochondrial Ca²⁺ related physiology and pathogenesis simultaneously in two distinct intracellular compartments.