A comparative evaluation of the strengths and potential caveats of the microglial inducible CreER mouse models

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....

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Main Authors: Alicia M. Bedolla, Gabriel L. McKinsey, Kierra Ware, Nicolas Santander, Thomas D. Arnold, Yu Luo
Format: Article
Language:English
Published: Elsevier 2024-01-01
Series:Cell Reports
Subjects:
Online Access:http://www.sciencedirect.com/science/article/pii/S2211124723016716
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author Alicia M. Bedolla
Gabriel L. McKinsey
Kierra Ware
Nicolas Santander
Thomas D. Arnold
Yu Luo
author_facet Alicia M. Bedolla
Gabriel L. McKinsey
Kierra Ware
Nicolas Santander
Thomas D. Arnold
Yu Luo
author_sort Alicia M. Bedolla
collection DOAJ
description 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.
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spelling doaj.art-972922c14d7b45af80e53857386cf4202024-01-14T05:38:19ZengElsevierCell Reports2211-12472024-01-01431113660A comparative evaluation of the strengths and potential caveats of the microglial inducible CreER mouse modelsAlicia M. Bedolla0Gabriel L. McKinsey1Kierra Ware2Nicolas Santander3Thomas D. Arnold4Yu Luo5Department of Molecular and Cellular Biosciences, University of Cincinnati, Cincinnati, OH 45229, USA; Neuroscience Graduate Program, University of Cincinnati, Cincinnati, OH 45229, USADepartment of Pediatrics, University of California, San Francisco, San Francisco, CA 94143, USA; Cardiovascular Research Institute, University of California, San Francisco, San Francisco, CA 94158, USADepartment of Molecular and Cellular Biosciences, University of Cincinnati, Cincinnati, OH 45229, USAInstituto de Ciencias de la Salud, Universidad de O’Higgins, Rancagua, ChileDepartment of Pediatrics, University of California, San Francisco, San Francisco, CA 94143, USA; Cardiovascular Research Institute, University of California, San Francisco, San Francisco, CA 94158, USADepartment 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 authorSummary: 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.http://www.sciencedirect.com/science/article/pii/S2211124723016716CP: Neuroscience
spellingShingle Alicia M. Bedolla
Gabriel L. McKinsey
Kierra Ware
Nicolas Santander
Thomas D. Arnold
Yu Luo
A comparative evaluation of the strengths and potential caveats of the microglial inducible CreER mouse models
Cell Reports
CP: Neuroscience
title A comparative evaluation of the strengths and potential caveats of the microglial inducible CreER mouse models
title_full A comparative evaluation of the strengths and potential caveats of the microglial inducible CreER mouse models
title_fullStr A comparative evaluation of the strengths and potential caveats of the microglial inducible CreER mouse models
title_full_unstemmed A comparative evaluation of the strengths and potential caveats of the microglial inducible CreER mouse models
title_short A comparative evaluation of the strengths and potential caveats of the microglial inducible CreER mouse models
title_sort comparative evaluation of the strengths and potential caveats of the microglial inducible creer mouse models
topic CP: Neuroscience
url http://www.sciencedirect.com/science/article/pii/S2211124723016716
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