Cell-specific inducible gene recombination in postnatal inner ear supporting cells and glia.
Recent studies indicate that supporting cells play important roles in inner ear development, function, and regeneration after injury, but the molecular mechanisms underlying these processes remain poorly understood. Inducible cell-specific gene recombination in supporting cells could be a powerful tool to study the roles of specific molecules in these cells. Here we tested the feasibility, effectiveness, and cell specificity of inducible Cre-mediated gene recombination in the postnatal inner ear using mice that express an inducible form of Cre (CreER(T)) under the transcriptional control of the proteolipid protein (PLP) promoter. We assessed the pattern of tamoxifen-induced gene recombination in the inner ear using the ROSA26-LacZ reporter line, in which the beta-galactosidase gene is expressed only after Cre-mediated excision of a loxP-flanked stop cassette. Recombination was detected in cochlear inner phalangeal cells, supporting cells surrounding hair cells in vestibular maculae and cristae. Recombination also occurred in Schwann cells. We also found that this CreER(T) line can be used to increase and decrease the levels of expression of a trophic factor, brain-derived neurotrophic factor, specifically in supporting cells. These results show that PLP/CreER(T) mice are a powerful tool to dissect gene function in inner ear supporting cells.
Gómez-Casati
María Eugenia
ME
F.M. Kirby Neurobiology Center, Children's Hospital Boston, 3 Blackfan Circle, CLS Room 12256, Boston, MA 02115, USA.
Murtie
Joshua
J
Taylor
Bethany
B
Corfas
Gabriel
G
D000818:Animals; D018931:Antineoplastic Agents, Hormonal; D019208:Brain-Derived Neurotrophic Factor / Q000235:genetics; D007758:Ear, Inner / Q000166:cytology / Q000196:embryology / Q000502:physiology; D018507:Gene Expression Regulation, Developmental; D017930:Genes, Reporter; D018069:Hair Cells, Vestibular / Q000502:physiology; D019426:Integrases / Q000235:genetics; D007763:Lac Operon; D051379:Mice; D008822:Mice, Transgenic; D018991:Myelin Proteolipid Protein / Q000235:genetics; D009457:Neuroglia / Q000502:physiology*; D011401:Promoter Regions, Genetic / Q000235:genetics; D011995:Recombination, Genetic / Q000502:physiology*; D012583:Schwann Cells / Q000502:physiology*; D013629:Tamoxifen; D019076:Transgenes / Q000235:genetics
D018931:Antineoplastic Agents, Hormonal; D019208:Brain-Derived Neurotrophic Factor; D018991:Myelin Proteolipid Protein; D013629:Tamoxifen; C045073:Cre recombinase; D019426:Integrases