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The gene of the alpha-subunit of the acetylcholine receptor: molecular organisation and transcription in myasthenia-associated thymomas.

DNA and RNA were isolated from 5 thymomas of Myasthenia Gravis (MG) patients, from normal tissues, and from the TE671 cell line (which expresses a muscle type acetylcholine receptor, AChR). The cDNA of the alpha-subunit of the AChR, a 159 bp BglII/BstEII fragment encoding the main immunogenic region (MIR) and a 88 bp EcoRV/TaqI fragment encoding the mAb155 binding site (a cytoplasmic epitope of AChR) served as probes. Hybridizations were performed under both high and low stringent conditions. Southern blot analysis of genomic DNA, restricted with EcoRI, HindIII and BamHI/HindIII, showed a normal pattern of restriction fragments in all tissues investigated. In particular, in thymomas there was no deletion of exon 4 which encodes the MIR. Dot and Northern blot analysis of total RNA and mRNA revealed transcription of the alpha-subunit AChR gene in TE671 cells and skeletal muscle but not in other tissues including thymomas. These results confirm former reports that there are no intact AChR in thymomas of MG patients. In addition we show here that there is also no truncated, MIR-deficient AChR or a protein with extensive molecular homology with the AChR in thymomas. These investigations support our idea that an AChR-unrelated protein might play a role in the pathogenesis of thymoma-associated MG [Marx et al., this volume].