Abstract
SummaryThe recent proliferation of newCreandCreERrecombinase 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 microglialCreERlines (Cx3cr1CreER(Litt),Cx3cr1CreER(Jung),P2ry12CreER,Tmem119CreER), focusing on (1) recombination specificity; (2) leakiness - degree of non-tamoxifen recombination in microglia and other cells; (3) efficiency of tamoxifen-induced recombination; (4) extra-neural recombination -the degree of recombination in cells outside the CNS, particularly myelo/monocyte lineages (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.
Publisher
Cold Spring Harbor Laboratory
Reference49 articles.
1. Carroll, J. A. , Race, B. , Williams, K. , Striebel, J. F. & Chesebro, B . Innate immune responses after stimulation with Toll-like receptor agonists in ex vivo microglial cultures and an in vivo model using mice with reduced microglia. J Neuroinflammation 18, 194 (2021).
2. Resting Microglial Cells Are Highly Dynamic Surveillants of Brain Parenchyma in Vivo
3. Synaptic Pruning by Microglia Is Necessary for Normal Brain Development
4. The “quad-partite” synapse: Microglia-synapse interactions in the developing and mature CNS
5. Microglia express distinct M1 and M2 phenotypic markers in the postnatal and adult CNS in male and female mice;J. Neuroscience,2015