Genetic labeling reveals cellular expression pattern of neuregulin 1 in mouse forebrain

Abstract Neuregulin 1 (Nrg1) encodes a neurotrophic factor and is genetically associated with schizophrenia, bipolar disorder and major depression. NRG1 has been shown to play important roles in neurodevelopment and neurotransmission. However, the knowledge about the cellular expression pattern of Nrg1 in mouse forebrain remains controversial and inconclusive. Here we used CRISPR/Cas9 techniques to generate Nrg1Cre/+ knockin mice which express the Cre recombinase immediately before the stop codon of Nrg1 gene. By crossing the Nrg1Cre/+ mice with Ai14 reporter mice which express fluorescent protein tdTomato in a Cre-dependent manner, we generated Nrg1 reporter mice which express tdTomato in cells where Nrg1 gene is actively transcribed. Using fluorescence imaging and unbiased stereology, we revealed the cellular expression pattern of Nrg1 in mouse forebrain regions including the olfactory bulb, cerebral cortex, striatum and hippocampus. We further performed stereotaxic injection of adeno-associated virus (AAV) which express tdTomato in a Cre-dependent way into different forebrain regions of adult Nrg1Cre/+ mice, and thus explored the distribution and axon projection of Nrg1-positive cells. These results provide fundamental information needed for the study of Nrg1 function in mouse forebrain. Moreover, the Nrg1Cre/+ mice generated here may represent a useful tool to study the function of neuronal populations expressing Nrg1.