Inhibitory neurons are crucial for shaping and regulating the dynamics of the entire network, and disturbances in these neurons contribute to brain disorders. Despite the recent progress in genetic labeling techniques, the heterogeneity of inhibitory neurons requires the development of highly characterized tools that allow accurate, convenient, and versatile visualization of inhibitory neurons in the mouse brain. Here, we report a novel genetic technique to visualize the vast majority and/or sparse subsets of inhibitory neurons in the mouse brain without using techniques that require advanced skills. We developed several lines of Cre-dependent tdTomato reporter mice based on the vesicular GABA transporter (VGAT)-BAC, named VGAT-stop-tdTomato mice. The most useful line (line #54) was selected for further analysis based on two characteristics: the inhibitory neuron-specificity of tdTomato expression and the transgene integration site, which confers efficient breeding and fewer adverse effects resulting from transgene integration-related genomic disruption. Robust and inhibitory neuron-specific expression of tdTomato was observed in a wide range of developmental and cellular contexts. By breeding the VGAT-stop-tdTomato mouse (line #54) with a novel Cre driver mouse line, Galntl4-CreER, sparse labeling of inhibitory neurons was achieved following tamoxifen administration. Furthermore, another interesting line (line #58) was generated through the unexpected integration of the transgene into the X-chromosome and will be used to map X-chromosome inactivation of inhibitory neurons. Taken together, our studies provide new, well-characterized tools with which multiple aspects of inhibitory neurons can be studied in the mouse.
Pubmed ID: 29063602 RIS Download
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View all literature mentionsThis polyclonal targets mouse VGAT, 31-112 aa(BC052020)
View all literature mentionsThis monoclonal targets Reelin
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View all literature mentionsThis unknown targets Prokaryotic recombinant fusion protein corresponding to a 1086bp Ki67 motif-containing cDNA fragment
View all literature mentionsThis unknown targets GABA
View all literature mentionsThis unknown targets PAX6
View all literature mentionsThis polyclonal targets mouse tdTomato, 1-476 aa (KJ081243)
View all literature mentionsThis polyclonal targets mouse tdTomato, 1-476 aa (KJ081243)
View all literature mentionsThis unknown targets PAX6
View all literature mentionsThis monoclonal targets Calbindin D-28k
View all literature mentionsThis polyclonal targets mouse tdTomato, 1-476 aa (KJ081243)
View all literature mentionsThis monoclonal targets Somatostatin
View all literature mentions