Differential response of C57BL/6J mouse and DBA/2J mouse to optic nerve crush

Retinal ganglion cell (RGC) death is the final consequence of many blinding diseases, where there is considerable variation in the time course and severity of RGC loss. Indeed, this process appears to be influenced by a wide variety of genetic and environmental factors. In this study we explored the genetic basis for differences in ganglion cell death in two inbred strains of mice. We found that RGCs are more susceptible to death following optic nerve crush in C57BL/6J mice (54% survival) than in DBA2/J mice (62% survival). Using the Illumina Mouse-6 microarray, we identified 1,580 genes with significant change in expression following optic nerve crush in these two strains of mice. Our analysis of the changes occurring after optic nerve crush demonstrated that the greatest amount of change (44% of the variance) was due to the injury itself. This included changes associated with ganglion cell death, reactive gliosis, and abortive regeneration. The second pattern of gene changes (23% of the variance) was primarily related to differences in gene expressions observed between the C57BL/6J and DBA/2J mouse strains. The remaining changes in gene expression represent interactions between the effects of optic nerve crush and the genetic background of the mouse. We extracted one genetic network from this dataset that appears to be related to tissue remodeling. One of the most intriguing sets of changes included members of the crystallin family of genes, which may represent a signature of pathways modulating the susceptibility of cells to death. Differential responses to optic nerve crush between two widely used strains of mice were used to define molecular networks associated with ganglion cell death and reactive gliosis. These results form the basis for our continuing interest in the modifiers of retinal injury. 18 Samples: 9 per strain (C57BL/6J & DBA/2J); 3 conditions per strain视网膜神经节细胞（Retinal ganglion cell, RGC）死亡是多种致盲性疾病的最终病理结局，此类疾病中RGC丢失的时间进程与严重程度存在显著异质性。事实上，这一过程受多种遗传与环境因素共同调控。本研究针对两种近交系小鼠，探究了其神经节细胞死亡差异的遗传基础。实验结果显示，视神经钳伤后，C57BL/6J小鼠的RGC存活率为54%，低于DBA/2J小鼠的62%，即前者RGC更易发生死亡。本研究利用Illumina Mouse-6微阵列，在这两种小鼠品系中鉴定出1580个视神经钳伤后表达发生显著改变的基因。对视神经钳伤后基因表达变化的分析表明，占方差总量44%的最大表达变化来源于损伤本身，这其中涵盖了与RGC死亡、反应性胶质增生以及再生失败相关的表达改变。第二种基因表达变化模式（方差占比23%）主要与C57BL/6J与DBA/2J小鼠品系间的基础基因表达差异相关。剩余的基因表达变化则体现了视神经钳伤效应与小鼠遗传背景之间的交互作用。我们从该数据集中提取出一个疑似与组织重塑相关的遗传调控网络。最引人关注的变化之一包括晶状体蛋白（crystallin）家族基因成员，其或可作为调控细胞死亡易感性的通路特征标志物。本研究利用两种常用小鼠品系对视神经钳伤的差异应答，定义了与RGC死亡及反应性胶质增生相关的分子网络。本研究结果为后续针对视网膜损伤修饰因子的相关研究奠定了基础。本数据集共包含18个样本：两种小鼠品系（C57BL/6J与DBA/2J）各9个样本；每个品系下设3种实验条件。