Tamoxifen-inducible glia-specific Cre mice for somatic mutagenesis in oligodendrocytes and Schwann cells.
Inducible transgenesis provides a valuable technique for the analysis of gene function in vivo. We report the generation and characterization of mouse lines carrying glia lineage-specific transgenes expressing an improved variant of the tamoxifen-inducible Cre recombinase, CreERT2, where the recombinase is fused to a mutated ligand binding domain of the human estrogen receptor. Using a PLP-CreERT2 transgene, we have generated mice that show specific inducible Cre function, as analyzed by cross-breeding experiments into the Rosa26 Cre-LacZ reporter line, in developing and adult Schwann cells, in mature myelinating oligodendrocytes, and in undifferentiated NG2-positive oligodendrocyte precursors in the adult. Using a P0Cx-CreERT2 transgene, we have also established mouse lines with inducible Cre function specifically in the Schwann cell lineage. These tamoxifen-inducible CreERT2 lines will allow detailed spatiotemporally controlled analysis of gene functions in loxP-based conditional mutant mice in both developing and adult Schwann cells and in the oligodendrocyte lineage.
Leone
Dino P
DP
Institute of Cell Biology, Department of Biology, Swiss Federal Institute of Technology, ETH Hönggerberg, Zürich, Switzerland.
Genoud
Stéphane
S
Atanasoski
Suzana
S
Grausenburger
Reinhard
R
Berger
Philipp
P
Metzger
Daniel
D
Macklin
Wendy B
WB
Chambon
Pierre
P
Suter
Ueli
U
D000818:Animals; D000831:Animals, Newborn; D001921:Brain / Q000166:cytology / Q000187:drug effects / Q000254:growth & development; D019070:Cell Lineage / Q000235:genetics; D004305:Dose-Response Relationship, Drug; D005260:Female; D005333:Fetus; D005786:Gene Expression Regulation / Q000235:genetics*; D017930:Genes, Reporter / Q000235:genetics; D019426:Integrases / Q000235:genetics*; D007774:Lactation / Q000187:drug effects; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D016296:Mutagenesis / Q000187:drug effects / Q000235:genetics*; D009836:Oligodendroglia / Q000187:drug effects / Q000378:metabolism*; D017933:Peripheral Nervous System / Q000166:cytology / Q000187:drug effects / Q000254:growth & development; D017434:Protein Structure, Tertiary / Q000235:genetics; D011960:Receptors, Estrogen / Q000235:genetics; D011993:Recombinant Fusion Proteins; D012583:Schwann Cells / Q000187:drug effects / Q000378:metabolism*; D013234:Stem Cells / Q000166:cytology / Q000378:metabolism; D013629:Tamoxifen / Q000494:pharmacology*; D019076:Transgenes / Q000187:drug effects / Q000235:genetics*; D014764:Viral Proteins / Q000235:genetics*
D011960:Receptors, Estrogen; D011993:Recombinant Fusion Proteins; D014764:Viral Proteins; D013629:Tamoxifen; C045073:Cre recombinase; D019426:Integrases