A comparative analysis of microglial inducible Cre lines
Travis E. Faust,
Philip A. Feinberg,
Ciara O’Connor,
Riki Kawaguchi,
Andrew Chan,
Hayley Strasburger,
Maximilian Frosch,
Margaret A. Boyle,
Takahiro Masuda,
Lukas Amann,
Klaus-Peter Knobeloch,
Marco Prinz,
Anne Schaefer,
Dorothy P. Schafer
Affiliations
Travis E. Faust
Department of Neurobiology, Brudnick Neuropsychiatric Research Institute, University of Massachusetts Chan Medical School, Worcester, MA 01605, USA
Philip A. Feinberg
Department of Neurobiology, Brudnick Neuropsychiatric Research Institute, University of Massachusetts Chan Medical School, Worcester, MA 01605, USA
Ciara O’Connor
Department of Neurobiology, Brudnick Neuropsychiatric Research Institute, University of Massachusetts Chan Medical School, Worcester, MA 01605, USA
Riki Kawaguchi
Department of Psychiatry and Neurology, UCLA, Los Angeles, CA 90095, USA
Andrew Chan
Department of Neuroscience, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA
Hayley Strasburger
Department of Neuroscience, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA
Maximilian Frosch
Institute of Neuropathology, Medical Faculty, University of Freiburg, 79106 Freiburg, Germany
Margaret A. Boyle
Department of Neurobiology, Brudnick Neuropsychiatric Research Institute, University of Massachusetts Chan Medical School, Worcester, MA 01605, USA
Takahiro Masuda
Institute of Neuropathology, Medical Faculty, University of Freiburg, 79106 Freiburg, Germany; Division of Molecular Neuroimmunology, Medical Institute of Bioregulation, Kyushu University, Fukuoka 812-8582, Japan
Lukas Amann
Institute of Neuropathology, Medical Faculty, University of Freiburg, 79106 Freiburg, Germany
Klaus-Peter Knobeloch
Institute of Neuropathology, Medical Faculty, University of Freiburg, 79106 Freiburg, Germany; Signalling Research Centres BIOSS and CIBSS, University of Freiburg, 79104 Freiburg, Germany
Marco Prinz
Institute of Neuropathology, Medical Faculty, University of Freiburg, 79106 Freiburg, Germany; Center for Basics in NeuroModulation (NeuroModulBasics), Faculty of Medicine, University of Freiburg, 79106 Freiburg, Germany; Signalling Research Centres BIOSS and CIBSS, University of Freiburg, 79104 Freiburg, Germany
Anne Schaefer
Department of Neuroscience, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; Max Planck Institute for Biology of Ageing, 50931 Cologne, Germany
Dorothy P. Schafer
Department of Neurobiology, Brudnick Neuropsychiatric Research Institute, University of Massachusetts Chan Medical School, Worcester, MA 01605, USA; Corresponding author
Summary: Cre/loxP technology has revolutionized genetic studies and allowed for spatial and temporal control of gene expression in specific cell types. Microglial biology has particularly benefited because microglia historically have been difficult to transduce with virus or electroporation methods for gene delivery. Here, we investigate five of the most widely available microglial inducible Cre lines. We demonstrate varying degrees of recombination efficiency, cell-type specificity, and spontaneous recombination, depending on the Cre line and inter-loxP distance. We also establish best practice guidelines and protocols to measure recombination efficiency, particularly in microglia. There is increasing evidence that microglia are key regulators of neural circuits and major drivers of a broad range of neurological diseases. Reliable manipulation of their function in vivo is of utmost importance. Identifying caveats and benefits of all tools and implementing the most rigorous protocols are crucial to the growth of the field and the development of microglia-based therapeutics.
