Figure 6. Excision of human AR transgene from skeletal muscle rescues neuromuscular pathology without reducing AR protein aggregate burden in CNS of BAC fxAR121 mice.

(A) Quadriceps muscle sections from 18 week-old male non-transgenic littermate controls, BAC fxAR121 – HSA-Cre mice, and BAC fxAR121 mice were stained with hematoxylin and eosin (H&E) and NADH. H&E staining of non-transgenic muscle (left) shows normal fibers of similar shape and size, but BAC fxAR121 muscle (right) reveals significant atrophy, with most fibers of markedly reduced caliber. Sections of BAC fxAR121 – HSA-Cre muscle (middle) appear relatively normal, with most fibers of large caliber, though one area of smaller fibers is present. NADH staining of non-transgenic muscle (left) yields occasional dark-staining fibers, while NADH staining of BAC fxAR121 sections (right) uncovers collections of very dark-staining fibers, undergoing atrophy. Evidence for muscle fiber atrophy is only occasionally present in BAC fxAR121 – HSA-Cre mice (middle). Scale bar = 50 µm.

(B) H&E-stained spinal cord sections from 28 week-old male BAC fxAR121 mice, BAC fxAR121 – HSA-Cre mice, and non-transgenic littermate controls reveals that ventral horn neurons in the lumbar spinal cord are reduced in size in BAC fxAR121 males, and that this size reduction phenotype is rescued in BAC fxAR121 – HSA-Cre mice. Scale bar = 50 µm.

(C) Quantification of ventral horn neuron soma size and perimeter shown in (B), n = 3 / group. ***P < .001, ANOVA with post-hoc Tukey test. Error bars = s.e.m.

(D) AR immunostaining of frontal cortex from 28 week-old male BAC fxAR121 mice, BAC fxAR121 – HSA-Cre mice, and non-transgenic littermates reveals prominent nuclear inclusions in the cortex of both BAC fxAR121 and BAC fxAR121 – HSA-Cre mice (see inset for AR nuclear aggregates, which are visualized as dark brown puncta). Scale bar = 50 µm.