Fig. 7

The gain-of function phenotype for hCD33m is dominant over the suppressive function of hCD33M. a Expression of hCD33M on primary microglia isolated from WT (gray), hCD33M⁺ (red), hCD33m⁺ (blue) and hCD33M⁺ hCD33m⁺ (green) mice. b,c Expression of hCD33m on primary microglia isolated from WT (black), hCD33m⁺ (blue) and hCD33M⁺ hCD33m⁺ (green) mice. Staining was carried out (b) without and (c) with permeabilization. Isotype-stained cells are shown in grey. d Phagocytosis of aggregated fluorescent Aβ_1–42 in all four types of microglia: WT (blue), hCD33M⁺ (red), hCD33m⁺ (blue), and hCD33M⁺ hCD33m⁺ (green). Each cell type was tested in competition with WT CD45.1⁺ mice. Phagocytosis data is expressed as a relative percentage compared to WT CD45.1⁺ mice (N = 3). e Phagocytosis of aggregated fluorescent Aβ_1–42 in WT U937 cells transduced with hCD33M (red), hCD33m (blue), or neither (EV) (black). Phagocytosis data is expressed as a relative percentage compared to EV (N = 3). f Schematic of a mini gene of CD33 containing only the two introns between Exon1 and 2 (intron 2) and Exon2 and 3 (intron 3). Two mini genes were created with a C or T at the corresponding location of the rs12459419 SNP. g,h Extracellular expression levels of (g) hCD33M and (h) hCD33m in CD33^−/− U937 cells transduced with the CD33 mini gene containing the C and T allele. Isotype-stained cells are shown in grey. i Phagocytosis of aggregated fluorescent Aβ_1–42 in CD33^−/− U937 cells transduced with CD33 mini gene containing the C and T allele. Phagocytosis data is expressed as a relative percentage compared to C allele. (N = 3)