Fig. 1: Organismal-level phenotypes.

a,b, The size of male (a) and female (b) HSA^LR animals is increased compared with control WT. c, The human HSA transgene is expressed in the quadriceps and gastrocnemius of HSA^LR mice, but not in the muscles of WT mice. Slight but significant differences are detected in HSA transgene expression between female and male HSA^LR muscles (n = 10, n = 15, n = 10, n = 23, for WT males and females and HSA^LR males and females respectively). This observation explains the effect of sex and interaction genotype × sex observed with ANOVA (Supplementary Fig. 2). d, Strong myotonia is observed in HSA^LR animals (n = 27, n = 3, n = 42, n = 11). e,f, Weight measurements show that females are smaller than males (n = 37, n = 15, n = 42, n = 19) (e), and normalization to WT weight shows that weight increases consistently in both male and female HSA^LR animals (f). g, Forelimb strength, measured in seconds, is comparable between males and females and significantly reduced in HSA^LR animals (n = 14, n = 15, n = 17, n = 19). h, Forelimb strength normalized to weight shows significant differences between sexes and genotypes. The boxes indicate the two central quartiles, the midline represents median values and the whiskers indicate the minimum and maximum data value, excluding outliers. Statistical analysis was performed using two-way ANOVA (WT versus HSA^LR, males versus females). Differences between WT and HSA^LR are represented as black asterisks. Differences between sexes were confirmed using the Wilcoxon test and are represented as blue asterisks. ***P < 0.001; **P < 0.01; *P < 0.05.