Western blot (WB) analysis of brain lysate isolated from Appw/w, Appδ7/δ7, Apph/h, Apps/s, and Appp/p rats with: (A) Y188, an antibody that detects mAPP, imAPP, αCTF, and βCTF. Specific APP signals are detected from all animals except the Appδ7/δ7 rats); (B) M3.2, a mouse monoclonal antibody that detects only rat WT APP and βCTF; (C) 6E10, a mouse monoclonal antibody that detects only APP and βCTF carrying the humanizing mutations. (D) WB analysis with anti-sAPPα and anti-sAPPβ-WT (absent in Appδ7/δ7 controls, *=non specific signal). (E–K) Quantification of APP metabolites in Apph/h and Appp/p rats normalized to GAPDH; APP levels as detected by either 6E10 (E) or Y188 (F); βCTF levels as detected by either 6E10 (G) or Y188 (H); αCTF levels as detected by Y188 (I); βCTF/αCTF ratio as measured by either 6E10-βCTF (J) or Y188-βCTF (K) quantitation values. Quantification of sAPPβ (L) and sAPPα (M) WB levels. (N) Aβ40 levels in Apph/h and Appp/p samples measured by Wako ELISA. Overexposed WBs are provided in panels A-B to show CTF levels clearly. Quantitations were performed on non-saturated exposures. Data are represented as mean ± SEM. Statistical analyses are by unpaired student’s t-test (*p<0.05; **p<0.01; ***p<0.001; ****p<0.0001). Animals were analyzed at p21. We used the following male and female animals: 2E, F, G, H, I, J, K, N; Apph/h, 2 males and 2 females; Appp/p, 2 males and 2 females: 2L and 2M; Apph/h, 3 males and 2 females; Appp/p, 3 males and 2 females.