To study the function of individual neurons that are embedded in a complex neural network is difficult in mice. Conditional mutagenesis permits the spatiotemporal control of gene expression. To direct expression of a tamoxifen-inducible variant of Cre recombinase (CreERT2) selectively to cortical projection neurons, we replaced the coding region of the murine Nex1 (Neurod6) gene by CreERT2 cDNA via homologous recombination in embryonic stem cells. When injected with tamoxifen, NEX-CreERT2 mice induced reporter gene expression exclusively in projection neurons of the neocortex and hippocampus. By titrating the tamoxifen dosage, we achieved recombination in single cells, which allows the analysis of individual cortical neurons, e.g. by confocal microscopy and multiphoton imaging in live mice.

Adult NEX-CreERT2 mice haboring a Cre-inducible tdtomato reporter were treated for 2 days with 100 mg/kg (high tam) or 25 mg/kg tamoxifen (low tam) and harvested 50 days later. Right: Confocal image of a neocortical projection neuron. Courtesy from T. Unterbarnscheidt

Detailed information in:

Agarwal A., Dibaj P., Kassmann C.M., Goebbels S., Nave K.A., Schwab M.H. (2012). In vivo imaging and non-invasive ablation of pyramidal neurons in adult NEX-CreERT2 mice. Cerebral Cortex 22: 1473-86.

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