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. 2023 Jul 1;31(9):2651–2661. doi: 10.1016/j.ymthe.2023.06.018

Figure 1.

Figure 1

TRPML1 gene transfer in PiZ livers reduces ATZ accumulation

(A) Schematic representation of AAV8 vectors injected in PiZ mice. (B) RT-PCR analysis for TRPML1 expression in livers of wild-type mice injected with AAV-GFP or AAV-TRPML1 (AAV-GFP, n = 7; AAV-TRPML1, n = 9). Human TRPML1 expression was normalized on murine Trpml1 mRNA. (C) Representative immunofluorescence staining for GFP, TRPML1, and TFEB in livers of PiZ mice injected with AAV vectors and harvested at 12 weeks post injection (n = 9 per group). Representative PAS-D (D) and Sirius Red (E) staining of livers of PiZ mice harvested 12 weeks after AAV injections and their corresponding quantifications (n = 9 per group). (F) Representative immunofluorescence staining for ATZ polymers in livers of PiZ mice injected with AAV vectors and harvested at 12 weeks post-injection. (G) Immunoblots for soluble and insoluble fractions on livers of PiZ mice injected with AAV-GFP or AAV-TRPML1 and their corresponding quantifications (AAV-GFP, n = 8; AAV-TRPML1, n = 9). GAPDH and H3 were used for normalization. AAV-GFP and AAV-TRPML1 are on the same gel but not contiguous. (H) Changes in percentages of serum total AAT (n = 9 per group) or polymeric ATZ (AAV-GFP, n = 6; AAV-TRPML1, n = 5; AAV-TFEB, n = 6) in PiZ mice after AAV injections. Data are shown as mean ± standard error. Student’s t test: ∗p value < 0.05; ∗∗p value < 0.01; ∗∗∗p value < 0.001. A.U., arbitrary units; p.i., post-injection.