Dystrophin and utrophin "double knockout" dystrophic mice exhibit a spectrum of degenerative musculoskeletal abnormalities.
Dystrophin and utrophin "double knockout" dystrophic mice exhibit a spectrum of degenerative musculoskeletal abnormalities.
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DOI：
10.1002/jor.22236
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发表时间：
2013-03
影响因子：
2.8
通讯作者：
Huard, Johnny
中科院分区：
文献类型：
--
作者：
Isaac, Christian;Wright, Adam;Usas, Arvydas;Li, Hongshuai;Tang, Ying;Mu, Xiaodong;Greco, Nicholas;Dong, Qing;Vo, Nam;Kang, James;Wang, Bing;Huard, Johnny
杜氏肌营养不良症（DMD）是一种退行性肌肉疾病，其特征在于肌纤维的肌膜处缺乏肌营养不良蛋白表达。此外，DMD患者获得骨质减少、脆性骨折和脊柱侧凸，表明骨骼稳态缺陷共存，但关于DMD对骨骼和肌肉骨骼系统内的其他结缔组织的影响知之甚少。最近的证据表明成人干细胞功能障碍与DMD的发病机制有关。鉴于肌肉和骨骼的共同间充质来源，我们试图在DMD小鼠模型中研究骨骼和其他肌肉骨骼组织。在这里，我们报告说，肌营养不良蛋白-肌营养不良蛋白双基因敲除（dko）小鼠表现出一系列的退行性变化，骨骼肌外，在骨，关节软骨，椎间盘，除了减少寿命，肌肉变性，脊柱畸形，心肌病先前报道。我们还报告这些小鼠具有降低的骨愈合能力，并在后肢肌肉中表现出自发性异位骨化。因此，我们提出dko小鼠作为过早肌肉骨骼老化的模型，并证实DMD患者可能发生类似的现象。
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.
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影响因子：
4.1
作者：
ANDERSON, JE;LENTZ, DL;JOHNSON, RB
通讯作者：
JOHNSON, RB
影响因子：
5.8
作者：
Boot, AM;deRidder, MAJ;KeizerSchrama, SMPFD
通讯作者：
KeizerSchrama, SMPFD
影响因子：
4.4
作者：
CARNWATH, JW;SHOTTON, DM
通讯作者：
SHOTTON, DM
影响因子：
64.5
作者：
Grady, RM;Teng, HB;Sanes, JR
通讯作者：
Sanes, JR
DOI：
10.1111/j.1365-2990.1988.tb00866.x
发表时间：
1988-01-01
影响因子：
5
作者：
COULTON, GR;MORGAN, JE;SLOPER, JC
通讯作者：
SLOPER, JC