Granchelli J A, Pollina C, Hudecki M S
Department of Biological Sciences, University at Buffalo, NY 14260-1300, USA.
J Neurol Sci. 1995 Jul;131(1):1-7. doi: 10.1016/0022-510x(95)00089-k.
Dystrophin-deficient female mdx mice were bred with male Tsk+/+ pa mice to examine the role played by mast cells in the pathophysiology of dystrophin deficiency. Resultant mdx/Tsk double-mutant mice were then examined functionally, biochemically, and histologically. While mdx mice remained as strong as their normal counterparts, mdx/Tsk double-mutant mice became progressively weak with age. Serum creatine kinase activity was significantly elevated in both mdx and mdx/Tsk double-mutant mice over normal controls. However, mast cell-derived plasma tryptase activity was consistently higher in the double-mutant than in mdx mice. In addition, histological examination of gastrocnemius muscle revealed that while necrosis was persistent in both strains of mdx mice from 2 to 8 weeks of age, regeneration was significantly reduced in the double-mutant mice. Of particular interest was the fact that necrosis in the mdx/Tsk double mutant exceeded mdx values at 8 weeks of age, corresponding approximately with a second peak in tryptase activity. Therefore, heightened mast cell activity appears to elicit in the dystrophin-deficient mdx mouse a myopathy not unlike the human Duchenne disease.
将肌营养不良蛋白缺陷的雌性mdx小鼠与雄性Tsk+/+ pa小鼠进行杂交，以研究肥大细胞在肌营养不良蛋白缺乏的病理生理学中所起的作用。然后对所得的mdx/Tsk双突变小鼠进行功能、生化和组织学检查。mdx小鼠仍与其正常同窝小鼠一样强壮，而mdx/Tsk双突变小鼠却随着年龄的增长逐渐变弱。与正常对照组相比，mdx和mdx/Tsk双突变小鼠的血清肌酸激酶活性均显著升高。然而，双突变小鼠中肥大细胞衍生的血浆类胰蛋白酶活性始终高于mdx小鼠。此外，对腓肠肌的组织学检查显示，虽然两种mdx小鼠品系在2至8周龄时坏死持续存在，但双突变小鼠的再生明显减少。特别有趣的是，mdx/Tsk双突变体在8周龄时的坏死超过了mdx小鼠的值，这大约与类胰蛋白酶活性的第二个峰值相对应。因此，肥大细胞活性增强似乎在肌营养不良蛋白缺陷的mdx小鼠中引发了一种类似于人类杜氏病的肌病。
