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Background  Pharmacologic control of Cre-mediated recombination using tamoxifen-dependent activation of a Cre-estrogen receptor ligand binding domain fusion protein [CreER(T)] is widely used to modify and/or visualize cells in the mouse.    Methods and Findings  We describe here two new mouse lines, constructed by gene targeting to the  Rosa26  locus to facilitate Cre-mediated cell modification. These lines should prove particularly useful in the context of sparse labeling experiments. The  R26rtTACreER  line provides ubiquitous expression of CreER under transcriptional control by the tetracycline reverse transactivator (rtTA); dual control by doxycycline and tamoxifen provides an extended dynamic range of Cre-mediated recombination activity. The  R26IAP  line provides high efficiency Cre-mediated activation of human placental alkaline phosphatase (hPLAP), complementing the widely used, but low efficiency,  Z/AP  line. By crossing with mouse lines that direct cell-type specific CreER expression, the  R26IAP  line has been used to produce atlases of labeled cholinergic and catecholaminergic neurons in the mouse brain. The  R26IAP  line has also been used to visualize the full morphologies of retinal dopaminergic amacrine cells, among the largest neurons in the mammalian retina.    Conclusions  The two new mouse lines described here expand the repertoire of genetically engineered mice available for controlled  in vivo  recombination and cell labeling using the Cre-lox system.

New Mouse Lines for the Analysis of Neuronal Morphology Using CreER(T)/loxP-Directed Sparse Labeling