Impaired recovery of dysferlin-null skeletal muscle after contraction-induced injury in vivo.
The protein, dysferlin, mediates sarcolemmal repair in vitro, implicating defective membrane repair in dysferlinopathies. To study the role of dysferlin in vivo, we assessed contractile function, sarcolemmal integrity, and myogenesis before and after injury from large-strain lengthening contractions in dysferlin-null and control mice. We report that dysferlin-null muscles produce higher contractile torque, and are equally susceptible to initial injury but recover from injury more slowly. Two weeks after injury, control muscles retain fluorescein dextran and do not show myogenesis. Dysferlin-null muscles do not retain fluorescein dextran, and show necrosis followed by myogenesis. Our data indicate that recovery of control muscles from injury primarily involves sarcolemmal repair whereas recovery of dysferlin-null muscles primarily involves myogenesis without repair and long-term survival of myofibers.
Roche
Joseph A
JA
Department of Physiology, University of Maryland School of Medicine, Baltimore, Maryland 21201, USA.
Lovering
Richard M
RM
Bloch
Robert J
RJ
D000818:Animals; D003911:Dextrans / Q000737:chemistry / Q000378:metabolism; D000073939:Dysferlin; D005452:Fluoresceins / Q000737:chemistry / Q000378:metabolism; D008297:Male; D008565:Membrane Proteins / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D051379:Mice; D008805:Mice, Inbred A; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D018613:Microscopy, Confocal; D008856:Microscopy, Fluorescence / Q000379:methods; D009119:Muscle Contraction / Q000502:physiology*; D024510:Muscle Development / Q000502:physiology; D018482:Muscle, Skeletal / Q000293:injuries / Q000378:metabolism / Q000503:physiopathology*; D020127:Recovery of Function / Q000502:physiology*; D012508:Sarcolemma / Q000378:metabolism; D019415:Torque; D014945:Wound Healing / Q000502:physiology
D003911:Dextrans; C497505:Dysf protein, mouse; D000073939:Dysferlin; D005452:Fluoresceins; D008565:Membrane Proteins; C052526:fluorescein-dextran