title: Integrated analysis of proteome and transcriptome changes in the mucopolysaccharidosis type VII mouse hippocampus.
abstract: 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.
authors.affiliation: Research Institute of the Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA.
authors.forename: Michael K
authors.initials: MK
authors.lastname: Parente
authors.affiliation: Research Institute of the Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA.
authors.forename: Ramona
authors.initials: R
authors.lastname: Rozen
authors.affiliation: Research Institute of the Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA.
authors.forename: Steven H
authors.initials: SH
authors.lastname: Seeholzer
authors.affiliation: 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. Electronic address: jhwolfe@vet.upenn.edu.
authors.forename: John H
authors.initials: JH
authors.lastname: Wolfe
mesh_terms: D000818:Animals; D020869:Gene Expression Profiling / Q000379:methods*; D005786:Gene Expression Regulation; D053263:Gene Regulatory Networks; D006624:Hippocampus / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D058977:Molecular Sequence Annotation; D016538:Mucopolysaccharidosis VII / Q000235:genetics* / Q000378:metabolism*; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods; D040901:Proteomics / Q000379:methods*; D053719:Tandem Mass Spectrometry
keywords: GUSB; Hippocampus; Lysosomal storage disease; MPS VII; Mitochondria; Mucopolysaccharidosis type VII; Neurodegeneration; Proteomic analysis; Transcriptome; β-Glucuronidase