title: APP(DeltaNL695) expression in murine tissue downregulates CNBP expression.
abstract: The cellular nucleic acid binding protein (CNBP) is a ubiquitously expressed protein involved in regulation of transcription and translation. CNBP, and its encoding gene ZNF9, have been shown to be involved in type 2 myotonic dystrophy. Both Alzheimer's disease (AD) and sporadic inclusion body myositis (sIBM) are age-related degenerative diseases associated with the accumulation of beta-amyloid. Overexpression of amyloid precursor protein (APP) in mice has been used to generate models of both diseases. We show here that overexpression of APP in skeletal muscle from a mouse model of sIBM reduces the expression of CNBP significantly. We examined CNBP expression in a brain-specific APP-overexpressing strain, and a whole body APP knock-in strain, and found that there was a reduction in CNBP expression in tissue expressing APP(Swe). We conclude that expression of APP(Swe) in murine tissue induces a decrease in CNBP expression. This effect does not appear to be due to alterations in CNBP transcription. APP(Swe) expression may provide a tool for the study of CNBP regulation and clues to the roles of both proteins in disease.
authors.affiliation: Department of Molecular and Cellular Biochemistry, University of Kentucky, Lexington, KY, USA.
authors.forename: Dana M
authors.initials: DM
authors.lastname: Niedowicz
authors.forename: Tina L
authors.initials: TL
authors.lastname: Beckett
authors.forename: Chris J
authors.initials: CJ
authors.lastname: Holler
authors.forename: Adam M
authors.initials: AM
authors.lastname: Weidner
authors.forename: M Paul
authors.initials: MP
authors.lastname: Murphy
mesh_terms: D016564:Amyloid beta-Protein Precursor / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D015153:Blotting, Western; D001921:Brain / Q000378:metabolism* / Q000473:pathology; D015536:Down-Regulation; D055879:Gene Knock-In Techniques; D051379:Mice; D008822:Mice, Transgenic; D018482:Muscle, Skeletal / Q000378:metabolism* / Q000473:pathology; D018979:Myositis, Inclusion Body / Q000235:genetics / Q000378:metabolism; D016601:RNA-Binding Proteins / Q000096:biosynthesis*
chemical_list: D016564:Amyloid beta-Protein Precursor; D016601:RNA-Binding Proteins; C499012:Cnbp protein, mouse