Functional analysis of dystrophin isoforms using DMD-null mice

Duchenne型肌营养不良症(DMD)基因编码肌营养不良蛋白(dystrophin，DMD)，以及一些较短的亚型，已被证明在各种非肌肉组织中表达。到目前为止，各种dystrophin亚型的生理功能还不完全清楚。在本研究中，我们研究了DMD缺失小鼠中出现的表型变化，在这些小鼠中，所有dystrophin亚型的表达已经完全中断。中等缺失的小鼠是存活的，但表现出严重的肌肉肥大和营养不良，也有雄性不育。此外，我们还发现DMD基因缺失小鼠的犁鼻轴突有脱叉现象，部分脱叉的犁鼻轴突异常地进入主嗅球。这些结果表明，dystrophin亚型在小鼠的各种组织中发挥着不同的重要作用。

The Duchenne muscular dystrophy (DMD) gene encodes dystrophin, which is a protein defective in DMD patients, as well as a number of shorter isoforms, which have been shown to be expressed in various non-muscle tissues. As of yet, the physiological function of the various dystrophin isoforms is not fully understood. In the present study, we investigated phenotypic alterations appeared in the DMD-null mice, where expression of all dystrophin isoforms had been totally disrupted. The MID -null mice were viable but displayed severe muscular hypertrophy and dystrophy, and also male sterility. In addition, we found that vomeronasal axons in the DMD-null mice are defasciculated, and some of the defasciculated vomeronasal axons aberrantly entered into the main olfactory bulb. These results suggest that the dystrophin isoforms play various important roles in a variety of tissues in the mouse.