Nicotinic neuronal acetylcholine receptor alpha-3 subunit transcription in normal and myasthenic thymus

Thymic transcription of the alpha-3 subunit of the AChR was studied through sequencing and PCR analysis of thymic cDNA clones, Northern blotting, and ribonuclease protection assays. This analysis revealed at least three, 3' end sequence variants for the alpha-3 subunit as well as a variant that results from the alternative splicing of an antisense 122 bp Alu sequence between exons 5 and 6 of the normal transcript. The spliced Alu sequence not only shifts the exon 6 reading frame but also carries an in-frame stop codon. If translated, this variant transcript would produce a truncated peptide lacking the fourth transmembrane domain of the subunit and carrying a carboxy terminus dodecapeptide not found in any other known AChR subunit sequence. The putative variant subunit may lack biological activity and should differ antigenically from its normal counterpart. In comparing the normal, the MG hypertrophic, and the MG thymoma for transcription of the alpha-3 subunit and its 122 bp variant, it was found that there were no qualitative or quantitative changes in alpha-3 transcript expression in the MG hypertrophic thymi. Thymomas, however, showed an overall decrease in alpha-3 transcription and a comparative increase in beta-amyloid precursor transcription. The decrease in the levels of alpha-3 transcription in thymomas may be related to the proliferation of thymic epithelial cells.