Parente Michael K, Rozen Ramona, Seeholzer Steven H, Wolfe John H
Research Institute of the Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA.
Research Institute of the Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA; W. F. Goodman Center for Comparative Medical Genetics, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA; Department of Pediatrics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
Mol Genet Metab. 2016 May;118(1):41-54. doi: 10.1016/j.ymgme.2016.03.003. Epub 2016 Mar 7.
Mucopolysaccharidosis type VII (MPS VII) is a lysosomal storage disease caused by the deficiency of β-glucuronidase. In this study, we compared the changes relative to normal littermates in the proteome and transcriptome of the hippocampus in the C57Bl/6 mouse model of MPS VII, which has well-documented histopathological and neurodegenerative changes. A completely different set of significant changes between normal and MPS VII littermates were found in each assay. Nevertheless, the functional annotation terms generated by the two methods showed agreement in many of the processes, which also corresponded to known pathology associated with the disease. Additionally, assay-specific changes were found, which in the proteomic analysis included mitochondria, energy generation, and cytoskeletal differences in the mutant, while the transcriptome differences included immune, vesicular, and extracellular matrix changes. In addition, the transcriptomic changes in the mutant hippocampus were concordant with those in a MPS VII mouse caused by the same mutation but on a different background inbred strain.
黏多糖贮积症VII型（MPS VII）是一种由β-葡萄糖醛酸酶缺乏引起的溶酶体贮积病。在本研究中，我们比较了MPS VII的C57Bl/6小鼠模型海马蛋白质组和转录组相对于正常同窝小鼠的变化，该模型具有充分记录的组织病理学和神经退行性变化。在每个检测中，正常小鼠和MPS VII同窝小鼠之间发现了完全不同的一组显著变化。然而，两种方法生成的功能注释术语在许多过程中显示出一致性，这也与该疾病相关的已知病理学相对应。此外，还发现了特定检测的变化，在蛋白质组分析中，突变体中的这些变化包括线粒体、能量产生和细胞骨架差异，而转录组差异包括免疫、囊泡和细胞外基质变化。此外，突变体海马中的转录组变化与由相同突变但背景不同的近交系引起的MPS VII小鼠中的变化一致。
