Dysferlin expression after normal myoblast transplantation in SCID and in SJL mice
Dysferlin expression after normal myoblast transplantation in SCID and in SJL mice
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DOI：
10.1016/s0960-8966(01)00254-1
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发表时间：
2002-02-01
影响因子：
2.8
通讯作者：
Tremblay, JP
中科院分区：
文献类型：
--
作者：
Leriche-Guérin, K;Anderson, LVB;Tremblay, JP
肢体带状肌营养不良2B型和三好肌病都是由最近克隆的基因异铁蛋白突变引起的。在本研究中，我们研究了细胞移植是否可以在体内表达dysferlin。采用两种移植模型：SCID小鼠移植正常人成肌细胞，肢体带状肌营养不良2B型和三好肌病小鼠模型SJL小鼠移植异体原代小鼠肌细胞培养物，表达在肌钙蛋白i的肌肉启动子控制下的β -半乳糖苷酶基因。移植1个月后，在所有移植的SCID和SJL肌肉中分别检测到人和小鼠dysferlin蛋白。在成肌细胞移植后，观察到dysferlin和人肌营养不良蛋白或β -半乳糖苷酶阳性纤维的共定位。免疫细胞化学和Western blot检测Dysferlin蛋白。SCID和SJL肌肉切片中dysferlin阳性纤维的数量分别为40-50%和20-30%。SCID小鼠和dysferlin缺乏的SJL小鼠的dysferlin检测表明，成肌细胞移植允许供体dysferlin蛋白的表达。(C) 2002 Elsevier Science B.V.版权所有
Limb girdle muscular dystrophy type 2B form and Miyoshi myopathy are both caused by mutations in the recently cloned gene dysferlin. In the present study, we have investigated whether cell transplantation could permit dysferlin expression in vivo. Two transplantation models were used: SCID mice transplanted with normal human myoblasts, and SJL mice, the mouse model for limb girdle muscular dystrophy type 2B and Miyoshi myopathy, transplanted with allogeneic primary mouse muscle cell cultures expressing the beta -galactosidase gene under control of a muscle promoter of Troponin I. FK506 immunosuppression was used in the non-compatible allogeneic model. One month after transplantation, human and mouse dysferlin proteins were detected in all transplanted SCID and SJL muscles, respectively. Co-localization of dysferlin and human dystrophin or beta -galactosidase-positive fibers was observed following the transplantation of myoblasts. Dysferlin proteins were monitored by immunocytochemistry and Western blot. The number of dysferlin-positive fibers was 40-50% and 20-30% in SCID and SJL muscle sections, respectively. Detection of dysferlin in both SCID mice and dysferlin-deficient SJL mouse shows that myoblast transplantation permits the expression of the donor dysferlin protein. (C) 2002 Elsevier Science B.V. All rights reserved.