Dystrophin and utrophin "double knockout" dystrophic mice exhibit a spectrum of degenerative musculoskeletal abnormalities.

Abstract

Duchenne muscular dystrophy (DMD) is a degenerative muscle disorder characterized by the lack of dystrophin expression at the sarcolemma of muscle fibers. In addition, DMD patients acquire osteopenia, fragility fractures, and scoliosis indicating that a deficiency in skeletal homeostasis coexists but little is known about the effects of DMD on bone and other connective tissues within the musculoskeletal system. Recent evidence has emerged implicating adult stem cell dysfunction in DMD myopathogenesis. Given the common mesenchymal origin of muscle and bone, we sought to investigate bone and other musculoskeletal tissues in a DMD mouse model. Here, we report that dystrophin-utrophin double knockout (dko) mice exhibit a spectrum of degenerative changes, outside skeletal muscle, in bone, articular cartilage, and intervertebral discs, in addition to reduced lifespan, muscle degeneration, spinal deformity, and cardiomyopathy previously reported. We also report these mice to have a reduced capacity for bone healing and exhibit spontaneous heterotopic ossification in the hind limb muscles. Therefore, we propose the dko mouse as a model for premature musculoskeletal aging and posit that a similar phenomenon may occur in patients with DMD.

• Authors: Christian Isaac, Adam Wright, Arvydas Usas, Hongshuai Li, Ying Tang, Xiaodong Mu, Nicholas Greco, Qing Dong, Nam Vo, James Kang, Bing Wang, Johnny Huard
• Journal: Journal of orthopaedic research : official publication of the Orthopaedic Research Society (J Orthop Res) Vol. 31 Issue 3 Pg. 343-9 (Mar 2013) ISSN: 1554-527X [Electronic] United States
• PMID: 23097179 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, Non-P.H.S.)
• Copyright: Copyright © 2012 Orthopaedic Research Society.

Chemical References

• Dystrophin
• Utrophin

Topics

• Aging, Premature (genetics, pathology, physiopathology)
• Animals
• Bone Diseases, Metabolic (genetics, pathology, physiopathology)
• Calcinosis (genetics, pathology, physiopathology)
• Cardiomyopathies (genetics, pathology, physiopathology)
• Cartilage, Articular (pathology, physiopathology)
• Disease Models, Animal
• Disease Progression
• Dystrophin (genetics)
• Fracture Healing (physiology)
• Intervertebral Disc (pathology, physiopathology)
• Mice
• Mice, Inbred C57BL
• Mice, Inbred mdx
• Mice, Knockout
• Muscle, Skeletal (pathology, physiopathology)
• Muscular Dystrophy, Animal (genetics, pathology, physiopathology)
• Muscular Dystrophy, Duchenne (genetics, pathology, physiopathology)
• Tibial Fractures (pathology, physiopathology)
• Utrophin (genetics)