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

• Published in: The Journal of neuroscience Vol. 23; no. 6; pp. 2314 - 2322
• Main Authors: Badea, Tudor C, Wang, Yanshu, Nathans, Jeremy
• Format: Journal Article
• Language: English
• Published: United States Soc Neuroscience 15-03-2003; Society for Neuroscience
• Subjects: Alkaline Phosphatase - analysis; Alkaline Phosphatase - metabolism; Animals; Brain - cytology; Brain - growth & development; Cell Lineage - physiology; Clone Cells - classification; Clone Cells - cytology; Clone Cells - metabolism; Gene Targeting; Genes, Reporter; Histocytochemistry - methods; Integrases - genetics; Mice; Neurons - classification; Neurons - cytology; Neurons - metabolism; Phenotype; Receptors, Estrogen - genetics; Recombinant Fusion Proteins - drug effects; Recombinant Fusion Proteins - genetics; Recombinant Fusion Proteins - metabolism; Recombination, Genetic; Reproducibility of Results; Selective Estrogen Receptor Modulators - pharmacology; Tamoxifen - pharmacology; Transgenes; Viral Proteins - genetics
• ISSN: 0270-6474; 1529-2401
• DOI: 10.1523/jneurosci.23-06-02314.2003

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.