title: Cre recombinase expression or topical tamoxifen treatment do not affect retinal structure and function, neuronal vulnerability or glial reactivity in the mouse eye.
abstract: Mice with a constitutive or tamoxifen-induced Cre recombinase (Cre) expression are frequently used research tools to allow the conditional deletion of target genes via the Cre-loxP system. Here we analyzed for the first time in a comprehensive and comparative way, whether retinal Cre expression or topical tamoxifen treatment itself would cause structural or functional changes, including changes in the expression profiles of molecular markers, glial reactivity and photoreceptor vulnerability. To this end, we characterized the transgenic α-Cre, Lmop-Cre and the tamoxifen-inducible CAGG-CreER™ mouse lines, all having robust Cre expression in the neuronal retina. In addition, we characterized the effects of topical tamoxifen treatment itself in wildtype mice. We performed morphometric analyses, immunohistochemical staining, in vivo ERG and angiography analyses and realtime RT-PCR analyses. Furthermore, the influence of Cre recombinase or topical tamoxifen exposure on neuronal vulnerability was studied by using light damage as a model for photoreceptor degeneration. Taken together, neither the expression of Cre, nor topical tamoxifen treatment caused detectable changes in retinal structure and function, the expression profiles of investigated molecular markers, glial reactivity and photoreceptor vulnerability. We conclude that the Cre-loxP system and its induction through tamoxifen is a safe and reliable method to delete desired target genes in the neural retina.
authors.affiliation: Institute of Human Anatomy and Embryology, University of Regensburg, Germany.
authors.forename: S K
authors.initials: SK
authors.lastname: Boneva
authors.affiliation: Institute of Human Anatomy and Embryology, University of Regensburg, Germany.
authors.forename: T R
authors.initials: TR
authors.lastname: Groß
authors.affiliation: Institute of Human Anatomy and Embryology, University of Regensburg, Germany.
authors.forename: A
authors.initials: A
authors.lastname: Schlecht
authors.affiliation: Institute of Human Anatomy and Embryology, University of Regensburg, Germany.
authors.forename: S I
authors.initials: SI
authors.lastname: Schmitt
authors.affiliation: Institute of Human Anatomy and Embryology, University of Regensburg, Germany.
authors.forename: C
authors.initials: C
authors.lastname: Sippl
authors.affiliation: Department of Ophthalmology, University Clinic Regensburg, Germany.
authors.forename: H
authors.initials: H
authors.lastname: Jägle
authors.affiliation: Department of Ophthalmology, University Clinic Regensburg, Germany.
authors.forename: C
authors.initials: C
authors.lastname: Volz
authors.affiliation: Department of Medical and Molecular Genetics, King's College London, United Kingdom.
authors.forename: A
authors.initials: A
authors.lastname: Neueder
authors.affiliation: Institute of Human Anatomy and Embryology, University of Regensburg, Germany.
authors.forename: E R
authors.initials: ER
authors.lastname: Tamm
authors.affiliation: Institute of Human Anatomy and Embryology, University of Regensburg, Germany. Electronic address: Barbara.Braunger@ur.de.
authors.forename: B M
authors.initials: BM
authors.lastname: Braunger
mesh_terms: D000287:Administration, Topical; D000792:Angiography; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001253:Astrocytes / Q000187:drug effects* / Q000378:metabolism; D004596:Electroretinography; D005123:Eye / Q000098:blood supply / Q000000981:diagnostic imaging; D019426:Integrases / Q000378:metabolism / Q000633:toxicity*; D051379:Mice; D008822:Mice, Transgenic; D017628:Microglia / Q000187:drug effects* / Q000378:metabolism; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D012160:Retina / Q000033:anatomy & histology / Q000187:drug effects* / Q000502:physiology; D013629:Tamoxifen / Q000008:administration & dosage / Q000633:toxicity*
chemical_list: D013629:Tamoxifen; C045073:Cre recombinase; D019426:Integrases
keywords: Cre recombinase; macro- and microglia cell reactivity; neuronal vulnerability; neuroprotective factors; retinal neurons; tamoxifen