Figure 3.

Treadmill exercise causes muscle wasting in Col6a1^–/– mice. (A) Representative cross-sections of TA and diaphragm muscles stained with H & E or with histochemical reaction for SDH and isolated from 5-mo-old wild-type and Col6a1^–/– mice after 1 h treadmill exercise. H & E staining shows normal morphology in both muscles of wild-type animals after treadmill. Instead, TA from Col6a1^–/– mice after treadmill displays severe muscle degeneration characterized by inflammation (white asterisk), degenerating myofibers (white arrows), centrally nucleated fibers (black arrowheads), and atrophic myofibers (black arrows). The extent of muscle degeneration in the diaphragm of Col6a1^–/– mice after treadmill is similar to that observed in standard conditions. SDH staining of TA and diaphragm is normal in wild-type mice after treadmill. In Col6a1^–/– animals subjected to treadmill several abnormal poorly stained fibers (red asterisks) are present in TA, while the diaphragm displays an apparently normal SDH staining. Scale bar, 100 μm. (B) Representative IgG immunolabeling images of TA cross-sections from wild-type and Col6a1^–/– mice after 1 h of treadmill exercise, confirming extensive inflammation in Col6a1^–/– TA but not in the corresponding wild-type samples. Scale bar, 100 μm. (C) Electron micrographs of TA from wild-type and Col6a1^–/– mice after treadmill exercise. Col6a1^–/– TA displays a large number of severe ultrastructural alterations, while wild-type TA presents fibers with dilated sarcoplasmic reticulum and some altered mitochondria. Col6a1^–/– TA displays a marked accumulation of dilated sarcoplasmic reticulum (arrowheads) and abnormal mitochondria. Almost all Col6a1^–/– mitochondria appear fragmented and many of them with completely swollen cristae, while the majority of wild-type mitochondria maintain elongated shape and normal cristae morphology (lower panels). Scale bars, 1 μm. mit, mitochondria; WT, wild-type.