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. |