Figure 6.

p62 overexpression ameliorates behavioral and visible phenotypes in male AR–97Q mice. A, A schematic view of the transgene construct. The microinjected fragment was composed of a cytomegalovirus enhancer (E), a chicken β-actin promoter (Pro), full-length human p62 with an HA tag, and a rabbit β-globin polyadenylation signal sequence (polyA). B, Western blotting analysis of total spinal cord and muscle protein lysates from wild-type (Wt) and p62^(tg/+) mice immunolabeled with antibodies against p62 and HA. C, D, HA immunohistochemistry in the spinal anterior horn (C) and skeletal muscle (D) of 13-week-old wild-type (Wt) and p62^(tg/+) mice counterstained with Mayer's hematoxylin. p62 immunoreactivity localized to the nuclei and cytoplasms of anterior horn cells (C) and skeletal muscle (D). HA staining was absent in the wild-type mice. Scale bars, 50 μm. E–I, Rotarod task (E), cage activity (F), grip strength (G), body weight (H), and survival rate (I) of AR–97Q/p62^(+/+) (●; n = 25) and AR–97Q/p62^(tg/+)(▾; n = 21) mice. J, Footprints of representative 25-week-old AR–97Q/p62^(+/+) and AR–97Q/p62^(tg/+) mice. The front paws are indicated in blue, and the hindpaws are indicated in red. Values are expressed as the means ± SEM. *p < 0.01.