title: New mouse lines for the analysis of neuronal morphology using CreER(T)/loxP-directed sparse labeling.
abstract: 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.
  
  
  RESULTS
  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.
authors.affiliation: Department of Molecular Biology and Genetics, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA. tbadea@mail.jhmi.edu
authors.forename: Tudor C
authors.initials: TC
authors.lastname: Badea
authors.forename: Zhong L
authors.initials: ZL
authors.lastname: Hua
authors.forename: Philip M
authors.initials: PM
authors.lastname: Smallwood
authors.forename: John
authors.initials: J
authors.lastname: Williams
authors.forename: Thomas
authors.initials: T
authors.lastname: Rotolo
authors.forename: Xin
authors.initials: X
authors.lastname: Ye
authors.forename: Jeremy
authors.initials: J
authors.lastname: Nathans
mesh_terms: D000469:Alkaline Phosphatase / Q000378:metabolism; D000818:Animals; D001921:Brain / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004318:Doxycycline / Q000494:pharmacology; D005260:Female; D005818:Genetic Engineering / Q000379:methods; D019426:Integrases / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D008957:Models, Genetic; D009474:Neurons / Q000378:metabolism* / Q000473:pathology; D011995:Recombination, Genetic; D013629:Tamoxifen / Q000031:analogs & derivatives / Q000494:pharmacology; D015533:Transcriptional Activation; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism
chemical_list: D013629:Tamoxifen; C016601:afimoxifene; D014446:Tyrosine 3-Monooxygenase; C045073:Cre recombinase; D019426:Integrases; D000469:Alkaline Phosphatase; D004318:Doxycycline