Fig. 1: Early and persistent androgen-dependent overexpression of LSD1 and PRMT6 in the skeletal muscle of SBMA mice and patients. | Nature Communications

Fig. 1: Early and persistent androgen-dependent overexpression of LSD1 and PRMT6 in the skeletal muscle of SBMA mice and patients.

From: LSD1/PRMT6-targeting gene therapy to attenuate androgen receptor toxic gain-of-function ameliorates spinobulbar muscular atrophy phenotypes in flies and mice

Fig. 1: Early and persistent androgen-dependent overexpression of LSD1 and PRMT6 in the skeletal muscle of SBMA mice and patients.The alternative text for this image may have been generated using AI.

a RT-PCR analysis of Lsd1 and Prmt6 transcript levels in the indicated tissues of WT and AR100Q mice (mice/genotype/age: LSD1 n = 4; PRMT6: skeletal muscle n = 5 at 4 weeks, n = 4 at 8–12 weeks; liver: n = 3; heart, brainstem and spinal cord: n = 4). b Western blots of LSD1 and PRMT6 levels in the quadriceps muscle of 12-week-old WT and AR100Q mice (n = 4 mice/genotype). *p = 0.048 LSD1, and p = 0.023 PRMT6. LSD1 and PRMT6 were detected with specific antibodies, and calnexin (CNX) was used as loading control. c RT-PCR analysis of Lsd1 and Prmt6 transcript levels in the quadriceps muscle of female WT and AR100Q mice (n = 4 mice/genotype). d RT-PCR analysis of Lsd1 and Prmt6 transcript levels in the extensor digitorum longus muscle of sham-operated and surgically castrated 8-week-old male AR100Q mice (n = 3 WT and AR100Q sham-operated mice and n = 4 WT and AR100Q castrated mice). e RT-PCR analysis of Lsd1 and Prmt6 transcript levels in the quadriceps muscle of 24-week-old male WT and knock-in mice expressing AR113Q (n = 3 WT and 4 knock-in mice). f RT-PCR analysis of Lsd1 and Prmt6 transcript levels in C2C12 myoblasts stably transduced with empty lentiviral vector (mock) or vector expressing AR100Q and differentiated to myotubes in presence of DHT (10 nM, 10 days, LSD1 expression n = 4 biological replicates mock, and n = 6 biological replicates AR100Q; PRMT6 n = 5 biological replicates). g RT-PCR analysis of LSD1 and PRMT6 transcript levels of quadriceps muscle biopsies of control (CTR) subjects and SBMA patients (n = 5 participants/genotype). h (Left) Schematic of putative androgen-responsive elements in the promoter of Lsd1 and Prmt6. (Right) Chromatin-immunoprecipitation assays of AR occupancy at androgen-responsive elements (red bar) in C2C12 myoblasts expressing AR24Q or AR100Q treated with vehicle or DHT (10 nM, 12 h). Shown is one experiment representative of three technical replicates. Graphs show mean ± SEM; two-way ANOVA followed by Tukey HSD tests (a, c, d), or two-tailed Student t-test (b, e–h). Source data are provided as a Source data file.

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