title: A noninvasive genetic/pharmacologic strategy for visualizing cell morphology and clonal relationships in the mouse.
abstract: 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.
authors.affiliation: Department of Molecular Biology and Genetics, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA.
authors.forename: Tudor C
authors.initials: TC
authors.lastname: Badea
authors.forename: Yanshu
authors.initials: Y
authors.lastname: Wang
authors.forename: Jeremy
authors.initials: J
authors.lastname: Nathans
mesh_terms: D000469:Alkaline Phosphatase / Q000032:analysis / Q000378:metabolism; D000818:Animals; D001921:Brain / Q000166:cytology / Q000254:growth & development; D019070:Cell Lineage / Q000502:physiology; D002999:Clone Cells / Q000145:classification* / Q000166:cytology* / Q000378:metabolism; D018390:Gene Targeting; D017930:Genes, Reporter; D006651:Histocytochemistry / Q000379:methods*; D019426:Integrases / Q000235:genetics; D051379:Mice; D009474:Neurons / Q000145:classification* / Q000166:cytology* / Q000378:metabolism; D010641:Phenotype; D011960:Receptors, Estrogen / Q000235:genetics; D011993:Recombinant Fusion Proteins / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D011995:Recombination, Genetic; D015203:Reproducibility of Results; D020845:Selective Estrogen Receptor Modulators / Q000494:pharmacology; D013629:Tamoxifen / Q000494:pharmacology; D019076:Transgenes; D014764:Viral Proteins / Q000235:genetics
chemical_list: D011960:Receptors, Estrogen; D011993:Recombinant Fusion Proteins; D020845:Selective Estrogen Receptor Modulators; D014764:Viral Proteins; D013629:Tamoxifen; C045073:Cre recombinase; D019426:Integrases; D000469:Alkaline Phosphatase