Peterson A, Cross D
Ludwig Institute, Montreal, Quebec, Canada.
Adv Exp Med Biol. 1990;280:173-85. doi: 10.1007/978-1-4684-5865-7_20.
The nuclear-cytoplasmic relationships existing within mosaic muscle will likely determine whether myoblast transfer can effectively rescue diseased muscle. The mouse chimera preparation is one source of such mosaic muscle in which that in vivo relationship can be investigated in the complete absence of complicating immunological or surgical trauma. For several metabolic enzymes, the mature muscle fiber appears to contain a homogeneous mix of the proteins encoded by multiple myonuclei. This relationship is clearly not representative of all muscle proteins, as several examples of proteins highly localized to "nuclear territories" have now been described. Nonetheless, the intrafiber distribution of certain enzymes, particularly GP1-1, is appropriate for the basis of a genotype marking system applicable to mosaic fibers. In vitro rescue of mdg myotubes is readily achievable by incorporation of few normal myonuclei and possibly by only one. In vivo requirements are apparently far more stringent and an hypothesis in which the mdg gene product, a Ca+(+) channel subunit, is restricted to nuclear territories would be consistent with the disparate results obtained in vitro and in vivo. Finally, chimeras containing mdx/mdx cells may show a partial amelioration of muscle pathology and may provide a means of determining the minimum genetically normal myonuclear compliment required to prevent degeneration of dystrophin-deficient fibers.
嵌合肌肉中存在的核质关系可能会决定成肌细胞移植能否有效挽救患病肌肉。小鼠嵌合体的制备是这种嵌合肌肉的一个来源，通过它可以在完全不存在复杂的免疫或手术创伤的情况下研究体内这种关系。对于几种代谢酶而言，成熟的肌纤维似乎含有由多个肌核编码的蛋白质的均匀混合物。这种关系显然并不代表所有肌肉蛋白，因为现在已经描述了几种高度定位于“核区域”的蛋白质实例。尽管如此，某些酶，特别是GP1-1的纤维内分布，适合作为适用于嵌合纤维的基因型标记系统的基础。通过掺入少量正常肌核，甚至可能仅掺入一个正常肌核，就可以很容易地在体外挽救mdg肌管。体内需求显然要严格得多，一种假设认为mdg基因产物（一种Ca+(+)通道亚基）局限于核区域，这与在体外和体内获得的不同结果是一致的。最后，含有mdx/mdx细胞的嵌合体可能会显示出肌肉病理学的部分改善，并可能提供一种方法来确定防止抗肌萎缩蛋白缺陷纤维退化所需的最小基因正常肌核数量。
