Transcriptome assessment of the Pompe (Gaa-/-) mouse cervical cord confirms widespread neuropathology.. Mus musculus

The only FDA approved therapy for Pompe is directed at correcting skeletal and cardiac muscle pathology, however, clinical and animal model data show strong histological evidence for a neurological disease component. While neuronal cell death and neuroinflammation are prominent in many lysosomal disorders, these processes have not been evaluated in Pompe disease. There is also no information available regarding the impact of Pompe disease on the fundamental pathways associated with synaptic communication. We used microarrays to gain insight regarding pathogenetic signaling pathways that might contribute to neuropathology in Pompe (Gaa-/-) mice. Overall design: To test whether systemic absence of GAA protein activated signalling pathways associated with neuropathology, genomic data (Affymetrix Mouse Gene Array 2.0ST) from the mid-cervical spinal cord in 6-and 16-mo old Pompe (Gaa-/-) were evaluated.

目前美国食品药品监督管理局（Food and Drug Administration, FDA）获批的唯一针对庞贝病（Pompe disease）的治疗手段，均以纠正骨骼肌与心肌病理为目标，但临床与动物模型数据均显示，该病存在明确的组织病理学证据，表明其具有神经系统疾病表型。
尽管神经元死亡与神经炎症（neuroinflammation）在多种溶酶体疾病（lysosomal disorders）中均为显著的病理特征，但目前尚无针对庞贝病中此类病理过程的相关评估研究。
此外，目前也暂无关于庞贝病对突触通信（synaptic communication）相关核心通路产生影响的相关研究数据。
本研究采用基因芯片（microarrays）技术，对可能参与庞贝病（Gaa-/-）小鼠神经病理发生的致病信号通路进行了探究。
整体实验设计：为验证系统性缺失GAA蛋白是否会激活与神经病理相关的信号通路，本研究对6月龄及16月龄庞贝病（Gaa-/-）小鼠的颈中段脊髓样本的基因组表达数据进行了分析，所用芯片为Affymetrix小鼠基因芯片2.0ST。