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

doi:10.1016/j.celrep.2023.113031

A comparative analysis of microglial inducible Cre lines

Cell Rep. 2023 Sep 26;42(9):113031. doi: 10.1016/j.celrep.2023.113031. Epub 2023 Aug 26.

Authors

Affiliations

¹ Department of Neurobiology, Brudnick Neuropsychiatric Research Institute, University of Massachusetts Chan Medical School, Worcester, MA 01605, USA.
² Department of Psychiatry and Neurology, UCLA, Los Angeles, CA 90095, USA.
³ Department of Neuroscience, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
⁴ Institute of Neuropathology, Medical Faculty, University of Freiburg, 79106 Freiburg, Germany.
⁵ 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.
⁶ Institute of Neuropathology, Medical Faculty, University of Freiburg, 79106 Freiburg, Germany; Signalling Research Centres BIOSS and CIBSS, University of Freiburg, 79104 Freiburg, Germany.
⁷ 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.
⁸ 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.
⁹ Department of Neurobiology, Brudnick Neuropsychiatric Research Institute, University of Massachusetts Chan Medical School, Worcester, MA 01605, USA. Electronic address: dorothy.schafer@umassmed.edu.

Abstract

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.

Keywords: CP: Neuroscience; Cre/loxP; CreER; microglia; recombination.

Publication types

Research Support, Non-U.S. Gov't
Research Support, N.I.H., Extramural

MeSH terms

Animals
Gene Transfer Techniques
Integrases* / metabolism
Mice
Mice, Transgenic
Microglia* / metabolism

Substances

Cre recombinase
Integrases

Abstract

Publication types

MeSH terms

Substances

Grants and funding