CONVERSION OF MDX MYOFIBERS FROM DYSTROPHIN-NEGATIVE TO DYSTROPHIN-POSITIVE BY INJECTION OF NORMAL MYOBLASTS
CONVERSION OF MDX MYOFIBERS FROM DYSTROPHIN-NEGATIVE TO DYSTROPHIN-POSITIVE BY INJECTION OF NORMAL MYOBLASTS
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DOI：
10.1038/337176a0
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发表时间：
1989-01-12
期刊：
影响因子：
64.8
通讯作者：
KUNKEL, LM
中科院分区：
文献类型：
--
作者：
PARTRIDGE, TA;MORGAN, JE;KUNKEL, LM
我们对杜氏肌营养不良症的主要原因的理解的最新进展的一个重要推论1 -6，是验证真正的遗传同源物作为疾病的动物模型7，8，其中可以测试潜在的治疗方法。持续性骨骼肌坏死是人杜氏肌营养不良症9的特征，在mdx小鼠中也观察到10 - 13，这两种情况都是肌营养不良蛋白缺乏的结果6，7，可能在肌纤维本身14 -16中。由于一种基因型的注射肌肉前体细胞可以与不同基因型的宿主肌纤维融合并表达供体基因17，18，我们决定测试正常肌肉前体细胞的移植物，以观察它们是否可以诱导先天性肌营养不良蛋白缺陷mdx肌纤维中肌营养不良蛋白的合成。我们表明，注射的正常肌肉前体细胞可以与预先存在或再生的mdx肌纤维融合，使其中许多纤维呈肌营养不良蛋白阳性，从而部分或全部将它们从生化缺陷中拯救出来。
An important corollary to the recent advances in our understanding of the primary cause of Duchenne muscular dystrophy1–6, is the validation of genuine genetic homologues as animal models of the disease7,8in which potential therapies can be tested. The persistent skeletal muscle necrosis that characterizes human Duchenne muscular dystrophy9is also seen in the mdx mouse10–13and is, in both, a consequence of a deficiency of dystrophin6,7, probably within the muscle fibres themselves14–16. As injected muscle precursor cells of one genotype can fuse with host muscle fibres of a different genotype and express the donor genes17,18, we decided to test grafts of normal muscle precursor cells to see if they could induce synthesis of dystrophin in innately dystrophin-deficient mdx muscle fibres. We show that injected normal muscle precursor cells can fuse with pre-existing or regenerating mdx muscle fibres to render many of these fibres dystrophin-positive and so to partially or wholly rescue them from their biochemical defect.