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Gattenlohner, S; Schneider, C; Thamer, C; Klein, R; Roggendorf, W; Gohlke, F; Niethammer, C; Czub, S; Vincent, A; Muller-Hermelink, HK; Marx, A.
Expression of foetal type acetylcholine receptor is restricted to type 1 muscle fibres in human neuromuscular disorders.
Brain. 2002; 125(Pt 6):1309-1319 Doi: 10.1093/brain/awf136 [OPEN ACCESS]
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Leading authors Med Uni Graz: Gattenlöhner Stefan
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Abstract:: In adult muscle, acetylcholine receptors (AChR) are restricted mainly to the motor endplate where the adult isoform (alphabetadeltaepsilon) is expressed. When skeletal muscle is denervated in animal models, there is atrophy of the muscle and a marked increase in expression of the AChR foetal isoform (alphabetagammadelta) containing a gamma-subunit. Similar changes in AChR expression are thought to occur in human muscle. While the role of denervation in regulating AChR gene expression has been widely studied, it has not been determined whether the transcriptional programmes responsible for defining different fibre types have an impact on the expression of AChR genes. We investigated biopsies from patients with a wide spectrum of neuromuscular diseases for expression of the AChR alpha- and gamma-subunits using RNase protection assays, alpha/gamma-duplex reverse transcriptase polymerase chain reaction, immunohistochemistry for foetal AChR and RNA in situ hybridization. Muscle from all patients with neurogenic disorders and, to a lesser extent, myogenic disorders, exhibited markedly increased transcription of the AChR gamma-subunit but, in contrast to previous animal studies, did not show increased AChR alpha-subunit. Moreover, both immunohistochemistry and RNA in situ hybridization revealed that AChR gamma-subunit hyperexpression occurred exclusively in atrophic type 1 and not in atrophic type 2 muscle fibres, irrespective of the underlying neuromuscular disease. We conclude that up-regulation of the AChR gamma-subunit in human muscle disorders is restricted to type 1 muscle fibres and, therefore, that AChR gamma-subunit expression is controlled by a muscle fibre type-restricted transcriptional programme. The factors influencing expression of this and other functional proteins should be relevant to the understanding and treatment of a range of neuromuscular disorders.
Find related publications in this database (using NLM MeSH Indexing): Atrophy -; Fetal Proteins - biosynthesis; Humans -; Muscle Fibers, Slow-Twitch - metabolism Muscle Fibers, Slow-Twitch - pathology; Neuromuscular Diseases - metabolism Neuromuscular Diseases - pathology; RNA, Messenger - biosynthesis; Receptors, Cholinergic - biosynthesis Receptors, Cholinergic - genetics; Transcription, Genetic -; Up-Regulation - physiology
Find related publications in this database (Keywords): acetylcholine receptor; muscle; fibre type; denervation; innervation