A comparative evaluation of the strengths and potential caveats of the microglial inducible CreER mouse models
Alicia M. Bedolla,
Gabriel L. McKinsey,
Kierra Ware,
Nicolas Santander,
Thomas D. Arnold,
Yu Luo
Affiliations
Alicia M. Bedolla
Department of Molecular and Cellular Biosciences, University of Cincinnati, Cincinnati, OH 45229, USA; Neuroscience Graduate Program, University of Cincinnati, Cincinnati, OH 45229, USA
Gabriel L. McKinsey
Department of Pediatrics, University of California, San Francisco, San Francisco, CA 94143, USA; Cardiovascular Research Institute, University of California, San Francisco, San Francisco, CA 94158, USA
Kierra Ware
Department of Molecular and Cellular Biosciences, University of Cincinnati, Cincinnati, OH 45229, USA
Nicolas Santander
Instituto de Ciencias de la Salud, Universidad de O’Higgins, Rancagua, Chile
Thomas D. Arnold
Department of Pediatrics, University of California, San Francisco, San Francisco, CA 94143, USA; Cardiovascular Research Institute, University of California, San Francisco, San Francisco, CA 94158, USA
Yu Luo
Department of Molecular and Cellular Biosciences, University of Cincinnati, Cincinnati, OH 45229, USA; Neuroscience Graduate Program, University of Cincinnati, Cincinnati, OH 45229, USA; Immunology Graduate Program, Cincinnati Children's Hospital Medical Center; Corresponding author
Summary: The recent proliferation of new Cre and CreER recombinase lines provides researchers with a diverse toolkit to study microglial gene function. To determine how best to apply these lines in studies of microglial gene function, a thorough and detailed comparison of their properties is needed. Here, we examined four different microglial CreER lines (Cx3cr1YFP-CreER(Litt), Cx3cr1CreER(Jung), P2ry12CreER, and Tmem119CreER), focusing on (1) recombination specificity, (2) leakiness (the degree of tamoxifen-independent recombination in microglia and other cells), (3) the efficiency of tamoxifen-induced recombination, (4) extraneural recombination (the degree of recombination in cells outside of the CNS, particularly myelo/monocyte lineages), and (5) off-target effects in the context of neonatal brain development. We identify important caveats and strengths for these lines, which will provide broad significance for researchers interested in performing conditional gene deletion in microglia. We also provide data emphasizing the potential of these lines for injury models that result in the recruitment of splenic immune cells.
