Weight and histopathological analyses of WT and homozygous VCP^R155H/R155H mice.

<p>(A) VCP^R155H/R155H mice are much smaller and weaker and demonstrate gross abnormalities such as hairless areas with ichthyosis-like thickening of the superficial layers of the skin compared to their WT littermates at day 14. MicroCT showed kyphosis of the homozygote mice. (B) Kaplan-Meier survival curve of WT and VCP^R155H/R155H mice. (C) Histogram demonstrating significant weight differences of WT and VCP^R155H/R155H mice. H&E images of (D) WT and (E) VCP^R155H/R155H mice demonstrating muscle pathology (Mag 63×). There was significant decrease in muscle mass with wide variation in muscle fiber size, central nuclei, split fibers and extensive fiber necrosis. Trichrome Gomori staining in (F) WT and (G) VCP^R155H/R155H mice revealed prominent staining in the periphery of the muscle fibers (Mag 63×). Histological H&E heart images of (H) WT (Mag 3200×) and (I) VCP^R155H/R155H mice (Mag 11000×) showing capillary dilations. EM analyses of quadriceps in (J) WT showing normal sarcomeric architecture (Mag 3200×) and (K) VCP^R155H/R155H mice revealing mitochondrial proliferation and architecture with megaconia and disrupted cristae (arrow) (Mag 11000×). EM analyses in (L) WT mice depicting normal heart histology and (M) VCP^R155H/R155H revealing enlarged vacuoles, highly disorganized and dilated vascular channels. EM analyses in (N) WT mice demonstrating normal brain histology (Mag 11000×) and (O) VCP^R155H/R155H revealing absence of well-defined synaptic complexes and post-synaptic enlargement in addition to vesicular degeneration (Mag 11000×).