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The Journal of Neuroscience, March 15, 2003, 23(6):2314

A Noninvasive Genetic/Pharmacologic Strategy for Visualizing Cell Morphology and Clonal Relationships in the Mouse

Tudor C. Badea¹, Yanshu Wang^{1, 4}, and Jeremy Nathans^{1, 2, 3, 4}

Departments of ¹ Molecular Biology and Genetics, ² Neuroscience, and ³ Ophthalmology, and ⁴ Howard Hughes Medical Institute, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205

Analysis of cellular morphology is the most general approach to neuronal classification. With the increased use of genetically engineered mice, there is a growing need for methods that can selectively visualize the morphologies of specified subsets of neurons. This capability is needed both to define cell morphologic phenotypes and to mark cells in a noninvasive manner for lineage studies. To this end, we describe a bipartite genetic system based on a Cre-estrogen receptor (ER) fusion protein that irreversibly activates a plasma membrane-bound alkaline phosphatase reporter gene by site-specific recombination. Because the efficiency and timing of gene rearrangement is controlled pharmacologically, a sparse subset of labeled cells can be generated from the set of CreER-expressing cells at any time during development. Histochemical visualization of alkaline phosphatase activity reveals neuronal morphology with strong and uniform labeling of all processes.

Key words: neuronal morphology; tamoxifen; Cre recombinase; lineage tracing; brain development; cell labeling

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Copyright © 2003 Society for Neuroscience  0270-6474/03/2362314-09$05.00/0

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