Fig. 1: APOE ‘switch mice’ efficiently transition from the expression of ApoE4 to ApoE2. | Nature Neuroscience

Fig. 1: APOE ‘switch mice’ efficiently transition from the expression of ApoE4 to ApoE2.

From: APOE4 to APOE2 allelic switching in mice improves Alzheimer’s disease-related metabolic signatures, neuropathology and cognition

Fig. 1: APOE ‘switch mice’ efficiently transition from the expression of ApoE4 to ApoE2.

a, Schematic depicting the genetic construct for the APOE4 to APOE2 ‘switch’ mouse (APOE4s2) and the experimental design for the experiments performed in APOE4s2 mice crossed to a globally (‘G’) expressed ROSA26-CreERT1 recombinase (APOE4s2G). Homozygous floxed Cre− littermates (APOE4s2) were used as controls. b,c, Allelic discrimination plots depicting a shift from APOE4 to APOE2 mRNA expression (b) in APOE4s2G mice in both the brain (b) and liver (c) compared to Cre− APOE4s2 littermates and ApoE2 and ApoE4 TR controls injected with TAM. d, Methodology used to semiquantitatively detect the ratio of peptides unique to E2 or E4 in the brain and plasma using liquid chromatography (LC)–MS/MS-based proteomic analysis. e,f, Ratio of unique E2 versus E4 peptides detected using LC–MS/MS-based proteomic analysis showing an efficient transition to E2 in both the brain (f) and plasma (g) of APOE4s2G (n = 4), APOE4s2 (n = 4), E2-TR (n = 2) and E4-TR (n = 2) mice. Data are represented as mean values ± s.e.m. RFU, relative fluorescence unit.

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