title: In vivo imaging and noninvasive ablation of pyramidal neurons in adult NEX-CreERT2 mice.
abstract: 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 including the ablation of cells by toxins. To direct expression of a tamoxifen-inducible variant of Cre recombinase (CreERT2) selectively to cortical neurons, we replaced the coding region of the murine Nex1 gene by CreERT2 cDNA via homologous recombination in embryonic stem cells. When injected with tamoxifen, adult 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 allowed multiphoton imaging of neocortical neurons in live mice. When hippocampal projection neurons were genetically ablated by induced expression of diphteria toxin, within 20 days the inflammatory response included the infiltration of CD3+ T cells. This marks a striking difference from similar studies, in which dying oligodendrocytes failed to recruit cells of the adaptive immune system.
authors: Department of Neurogenetics, Max Planck Institute of Experimental Medicine, 37075 Goettingen, Germany.
authors: Amit
authors: A
authors: Agarwal
authors: Payam
authors: P
authors: Dibaj
authors: Celia M
authors: CM
authors: Kassmann
authors: Sandra
authors: S
authors: Goebbels
authors: Klaus-Armin
authors: KA
authors: Nave
authors: Markus H
authors: MH
authors: Schwab
mesh_terms: D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics / Q000378:metabolism*; D002470:Cell Survival / Q000187:drug effects; D004167:Diphtheria Toxin / Q000506:poisoning*; D017930:Genes, Reporter; D019426:Integrases / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008822:Mice, Transgenic; D036641:Microscopy, Fluorescence, Multiphoton / Q000379:methods*; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D011042:Poisons / Q000494:pharmacology; D017966:Pyramidal Cells / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism*; D013629:Tamoxifen / Q000494:pharmacology*
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D004167:Diphtheria Toxin; D019426:Integrases; D009419:Nerve Tissue Proteins; D011042:Poisons; D011994:Recombinant Proteins; D013629:Tamoxifen; C110701:Neurod6 protein, mouse; C045073:Cre recombinase