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裸突变影响肢体骨骼肌发育。

Nude mutation influences limb skeletal muscle development.

作者信息

Morrison Jamie, Partridge Terence, Bou-Gharios George

机构信息

Muscle Cell Biology Group, MRC Clinical Research Building, Imperial College School of Medicine, Hammersmith Hospital, London W12 0NN, UK.

出版信息

Matrix Biol. 2005 Jan;23(8):535-42. doi: 10.1016/j.matbio.2004.10.003. Epub 2004 Dec 1.

Abstract

The nude mouse lacks functional T cells and other skin defects due to the absence of Foxn1 transcription factor. The mdx mouse bred onto a nude background (Foxn1-/-), to generate mdx nu/nu, serves as a valuable model for the use in muscle cell transplantation or gene therapy studies, to avoid a detrimental immune response. However, it has been shown previously that the mdx nu/nu mice have a skeletal muscle specific alteration in collagen production, which in the case of the limb muscles acts at or before the onset of the disease. This led to the conclusion that the nude mutation has an effect on the collagen deposition in skeletal muscles, which may be acting in a T cell independent manner. In an attempt to elucidate the role of the nude mutation on collagen production in skeletal muscles, we have measured collagen levels in several muscles of C57BL/10 nu/nu mice and compared them with mdx nu/nu and Foxn1+/+ control mice. We report here that the limb muscles of the young C57BL/10 nu/nu and mdx nu/nu mice contained a far higher proportion of collagen at an early age than Foxn1+/- control mice but regained normal levels by 12 weeks of age. This was largely attributable to the fact that 3 weeks old nude mice had considerably smaller limb muscles than Foxn1+/- mice which subsequently grew to normal size. We conclude that the nude mutation retards the early growth of development of muscle but not of the matrix tissue in limb muscles.

摘要

裸鼠由于缺乏Foxn1转录因子而缺乏功能性T细胞和存在其他皮肤缺陷。将mdx小鼠培育到裸鼠背景(Foxn1-/-)上,以产生mdx nu/nu小鼠,它可作为用于肌肉细胞移植或基因治疗研究的有价值模型,以避免有害的免疫反应。然而,先前已表明mdx nu/nu小鼠在胶原蛋白产生方面存在骨骼肌特异性改变,就肢体肌肉而言,这种改变在疾病发作时或之前就已出现。这导致得出结论,裸鼠突变对骨骼肌中的胶原蛋白沉积有影响,其可能以不依赖T细胞的方式起作用。为了阐明裸鼠突变对骨骼肌中胶原蛋白产生的作用,我们测量了C57BL/10 nu/nu小鼠几块肌肉中的胶原蛋白水平,并将它们与mdx nu/nu和Foxn1+/+对照小鼠进行比较。我们在此报告,年轻的C57BL/10 nu/nu和mdx nu/nu小鼠的肢体肌肉在早期含有的胶原蛋白比例远高于Foxn1+/-对照小鼠,但在12周龄时恢复到正常水平。这主要归因于3周龄的裸鼠肢体肌肉比Foxn1+/-小鼠小得多,而后者随后生长到正常大小。我们得出结论,裸鼠突变会延缓肢体肌肉中肌肉而非基质组织的早期生长发育。

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