Integrated analysis of proteome and transcriptome changes in the mucopolysaccharidosis type VII mouse hippocampus

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• 作者：Michael K. Parente^a ; ¹ ; Ramona Rozen^a ; ¹ ; ² ; Steven H. Seeholzer^a ; John H. Wolfe^a ; ^b ; ^c ; ^{jhwolfe@vet.upenn.edu" class="auth_mail" title="E-mail the corresponding author}
• 关键词：Mucopolysaccharidosis type VII ; MPS VII ; Lysosomal storage disease ; Transcriptome ; Proteomic analysis ; Mitochondria ; β-Glucuronidase ; GUSB ; Neurodegeneration ; Hippocampus
• 刊名：Molecular Genetics and Metabolism
• 出版年：2016
• 出版时间：May 2016
• 年：2016
• 卷：118
• 期：1
• 页码：41-54
• 全文大小：809 K

文摘

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.