BioCAT, Department of Biological Sciences, Illinois Institute of Technology, Chicago, IL 60616, USA.
Int J Mol Sci. 2018 Sep 6;19(9):2643. doi: 10.3390/ijms19092643.
Transgenic mouse models have been important tools for studying the relationship of genotype to phenotype for human diseases, including those of skeletal muscle. We show that mouse skeletal muscle can produce high quality X-ray diffraction patterns establishing the mouse intact skeletal muscle X-ray preparation as a potentially powerful tool to test structural hypotheses in health and disease. A notable feature of the mouse model system is the presence of residual myosin layer line intensities in contracting mouse muscle patterns. This provides an additional tool, along with the I/I intensity ratio, for estimating the proportions of active versus relaxed myosin heads under a given set of conditions that can be used to characterize a given physiological condition or mutant muscle type. We also show that analysis of the myosin layer line intensity distribution, including derivation of the myosin head radius, R, may be used to study the role of the super-relaxed state in myosin regulation. When the myosin inhibitor blebbistatin is used to inhibit force production, there is a shift towards a highly quasi-helically ordered configuration that is distinct from the normal resting state, indicating there are more than one helically ordered configuration for resting crossbridges.
转基因小鼠模型一直是研究人类疾病基因型与表型关系的重要工具，包括骨骼肌疾病。我们发现，小鼠骨骼肌可以产生高质量的 X 射线衍射图，这表明完整的小鼠骨骼肌 X 射线制备是一种潜在的强大工具，可以在健康和疾病状态下检验结构假说。小鼠模型系统的一个显著特点是，在收缩的小鼠肌肉模式中存在残留的肌球蛋白层线强度。这提供了另一种工具，与 I/I 强度比一起，用于估计在给定条件下活跃与松弛肌球蛋白头部的比例，可用于描述特定的生理状态或突变肌肉类型。我们还表明，肌球蛋白层线强度分布的分析，包括肌球蛋白头部半径 R 的推导，可用于研究超松弛状态在肌球蛋白调节中的作用。当使用肌球蛋白抑制剂 blebbistatin 抑制力的产生时，会出现向高度准螺旋有序构象的转变，这与正常的静息状态不同，表明静息交联桥有不止一种螺旋有序构象。
