Fig. 1
Disease progression and transgene expression in contemporary cohorts of male BAC fxAR121 mice. A Weight of BAC fxAR121 and wildtype male mice at 13 and 18 weeks, n = 8–13 mice/group. Two-tailed t-test, ***P < 0.001. B Grip strength of BAC fxAR121 and wildtype male mice at 13 and 18 weeks, n = 8–13 mice/group. Two-tailed t-test, ****P < 0.0001. C Terminal weight and grip strength metrics in 11–12 month-old BAC fxAR121 mice and controls, n = 5 mice/group. Two-tailed t-test, ****P < 0.0001. D Analysis of genomic polyQ length by PCR using DNA from mice born in 2010, 2014, and 2020. E Transgene (hAR) copy number analysis using genomic DNA from BAC fxAR121 mice born in 2010, 2014, and 2020, n = 4–5 mice/group. One-way ANOVA with post-hoc Tukey test, *P < 0.05, ***P < 0.001. F Weight of heterozygous (fx/WT) and homozygous (fx/fx) BAC fxAR121 mice at 12 and 18 weeks of age, n = 4–11 mice/group. Two-tailed t-test, **P<0.01. G Representative images of immunostaining performed on cross-sections of quadriceps muscle from 20 week-old male wildtype, BAC fxAR121 heterozygous (fx/WT), and BAC fxAR121 homozygous (fx/fx) mice. Laminin marking the outside of individual muscle fibers (green); nuclei (blue). Scale bar = 100 µm. H Kaplan–Meier survival analysis of heterozygous and homozygous BAC fxAR121 mice, n = 31–34 mice/group. Median survival of heterozygous BAC fxAR121fx/WT mice was 42.4 weeks, while median survival of homozygous BAC fxAR121fx/fx mice was 19.4 weeks. Log-rank Mantel-Cox test, ****P < 0.0001. I Western blot analysis of AR protein expression in quadriceps muscle of 15-week-old male BAC fxAR121 mice and wildtype controls born in 2019–2020. J Densitometry analysis of AR protein expression. Endogenous mouse AR (I, lower band) and polyQ human AR (I, upper band) are quantified separately and normalized to total protein, n = 6 mice/group. Two-tailed t-test, P = n.s. K Kaplan–Meier survival analysis of BAC fxAR121 mice born at Duke University between 2017 and 2020 compared to those born at UC Irvine between 2020 and 2022, n = 30–50 mice/group. Median survival of BAC fxAR121 mice born at Duke was 42.1 weeks, and median survival of mice born at UC Irvine was 40.6 weeks. Log-rank Mantel-Cox test, P = n.s. Error bars = s.e.m