Fig. 5. Systemic delivery of AAV9-AR45 did not induce detectable toxicity in mice expressing AR-2 at endogenous levels.

(A) Ratios of exogenous (exo) to endogenous (endo) AR45 mRNA copy number per ng of total RNA in TA muscle and lumbar spinal cord of four SBMA BAC transgenic mice 5 weeks after treatment with AAV9-AR45 (10¹¹ vg) are shown. (B) mRNA expression levels of exogenous AR45 in tissues of mice treated with AAV9-AR45 normalized to GAPDH housekeeping gene and expressed as fold change to levels in TA muscle are shown. Data are means ± SEM. Each dot represents one replicate (n = 3). (C) Representative cross sections of liver from adult wild-type and SBMA BAC transgenic mice treated with AAV9-control or AAV9-AR45 stained with F4/80 antibody and DAPI. Arrowheads indicate the F4/80 positive cells. Scale bars, 100 μm (low magnification) and 10 μm (high magnification). (D) Number of F4/80-positive cells per 100 cells is graphed. Quantification was performed from a total of six fields for all groups, three mice per treatment group. (E) mRNA expression levels of inflammatory and fibrotic marker genes in tissues from wild-type and SBMA BAC transgenic mice treated with AAV9-control or AAV9-AR45 normalized to GAPDH housekeeping gene and expressed as fold change to levels in the respective wild-type tissues are shown. Data are means ± SEM. Each dot represents one replicate (n = 3).