title: Muscle-specific overexpression of NCOATGK, splice variant of O-GlcNAcase, induces skeletal muscle atrophy.
abstract: The protein O-linked β-N-acetylglucosamine (O-GlcNAc) modification plays an important role in skeletal muscle development and physiological function. In this study, bitransgenic mice were generated that overexpressed NCOAT(GK), an O-GlcNAcase-inactive spliced variant of the O-GlcNAcase gene, specifically in skeletal muscle using the muscle creatine kinase promoter. Expression of the chimeric enhanced green fluorescent protein-NCOAT(GK) transgene caused an increase of cellular O-GlcNAc levels, along with the accumulation and activation of proapoptotic factors in muscles of bitransgenic mice. The consequence of overexpressing the transgene for a 2-wk period was muscle atrophy and, in some cases, resulted in the death of male mice. Muscle atrophy is a common complication of many diseases, some of which correlate markedly with high cellular O-GlcNAc levels, such as diabetes. Our study provides direct evidence linking muscle atrophy and the disruption of O-GlcNAcase activity.
authors.affiliation: Dept. of Medicine, Univ. of Alabama at Birmingham, Birmingham, AL 35294, USA.
authors.forename: Ping
authors.initials: P
authors.lastname: Huang
authors.forename: Shiuh-Rong
authors.initials: SR
authors.lastname: Ho
authors.forename: Kai
authors.initials: K
authors.lastname: Wang
authors.forename: Bryan C
authors.initials: BC
authors.lastname: Roessler
authors.forename: Fengxue
authors.initials: F
authors.lastname: Zhang
authors.forename: Yong
authors.initials: Y
authors.lastname: Hu
authors.forename: Damon B
authors.initials: DB
authors.lastname: Bowe
authors.forename: Jeffrey E
authors.initials: JE
authors.lastname: Kudlow
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Paterson
mesh_terms: D017398:Alternative Splicing / Q000235:genetics*; D000818:Animals; D051017:Apoptosis Regulatory Proteins / Q000235:genetics / Q000378:metabolism; D004195:Disease Models, Animal; D015971:Gene Expression Regulation, Enzymologic / Q000502:physiology; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D018485:Muscle Fibers, Skeletal / Q000378:metabolism / Q000473:pathology*; D018482:Muscle, Skeletal / Q000201:enzymology* / Q000473:pathology*; D009133:Muscular Atrophy / Q000201:enzymology* / Q000473:pathology*; D011401:Promoter Regions, Genetic / Q000235:genetics; D020033:Protein Isoforms / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D019076:Transgenes / Q000235:genetics; D015854:Up-Regulation / Q000235:genetics; D001619:beta-N-Acetylhexosaminidases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*
chemical_list: D051017:Apoptosis Regulatory Proteins; D020033:Protein Isoforms; C110628:hexosaminidase C; D001619:beta-N-Acetylhexosaminidases