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Table 1 Summary of the strengths and weaknesses of different mice models used to target microglia or border macrophages relative to their recombination efficiency using reporter mice. The data provided from the studies are either based on flow cytometry (FC) or immunofluorescence (IF) assays and this is precised for each point

From: Role of meningeal immunity in brain function and protection against pathogens

Model (line x reporter mouse used)

Strengths

Weaknesses

Tmem119-creERT2 x R26-TdT

• ~ 98% microglial recombination in adult and neonatal day 2 mice (IF/FC)

• Small to no recombination observed in PVM, pial and CP macrophages (FC/IF)

• No recombination in other parenchymal cell types (oligodendrocytes, astrocytes or neurons; IF).

• Small off-target effect on endothelium and pial cells

• 3% blood leukocytes still tagged 7 days after treatment.

P2ry12-creER x R26-TdT

• ~ 94% microglial recombination in adult (IF/FC)

• No effect on pial macrophages and PVM (IF).

• No recombination in other brain cell types (oligodendrocytes, astrocytes or neurons; IF).

• Limited off-target in other tissue macrophages and blood (IF/FC).

• 20% off-target effect on dural and CP macrophages (IF).

• 40% CP macrophages targeted when induced in embryonic day 13.5 (IF).

Cx3cr1-ccre: Sall1-ncre x R26-TdT

• ~ 88% recombination in microglia when the split-cre is homozygous (FC). No target of dural, pial, CP macrophages (IF) and other organs (IF/FC).

• 23% recombination in microglia in Cx3cr1-ccre: Sall1-ncre heterozygotes (FC).

Hexb-creERT2 x R26-YFP

• ~ 90% of microglial recombination observed in adults (FC/IF).

• Low recombination in PVM and subdural macrophages (0%), other brain cells, blood and other tissues (FC/IF).

• 60% off-target in the kidney if induced in adult (FC).

• No observation of the dura.

Cx3cr1-ccre: Lyve1-ncre x R26-TdT

• 60% recombination pial macrophage in Lyve1 homozygotes (IF).

• No recombination in choroid plexus macrophages (Lyve1-) (IF)

• 20% recombination in Lyve1 heterozygotes (IF).

• Recombination in some organs (heart, lung, adipose tissue) (FC/IF)

• Unknown effectiveness in the dura mater (some recombination observable but not quantified).

Cd163-cre x R26-YFP

• Recombination of 70% of dural macrophages and around 50–60% of brain macrophages (pial/CP/PVM) (FC)

• No off-target effect on the microglia (FC)

• Not specific to the CNS compartment (other peripheral organs express CD163)

Mrc1-creERT2 x R26-TdT

• ~ 95% PVM and pial macrophages targeted

• No recombination in other brain cell types (IF; oligodendrocytes, astrocytes or neurons), blood immune cells (FC).

• Heterozygotes and homozygotes have similar efficiency of recombination

• No observation of the dura

Pf4-Cre x R26-TdT

• 100% of perivascular, pial and dural macrophages (IF) and 80% of CP macrophages.

• ~ 5% microglia targeted (FC).

• Recombination in a neuronal population in the anterior amygdala and in other organs and platelets.