Thehumanmyelin basic protein geneisincluded within a 179-kilobase transcription unit: Expression inthe immuneandcentral nervous systems (multiple sclerosis/thymus/immunology/experinental allergc encephalomyelitis)

TwohumanGolli (for geneexpressed inthe oligodendrocyte lineage)-MBP (for myelin basic protein) cDNAs havebeenisolated fromahumanoligodendroglioma cell line. Analysis ofthese cDNAshasenabled ustodetermine theentire structure ofthehumanGolli-MBP gene. TheGofli-MBP gene, whichencompasses theMBP transcription unit, is=179kbin length andconsists of10exons, seven ofwhichconstitute the MBPgene. ThehumanGoli-MBP genecontains twotranscrip- tion start sites, eachofwhichgives rise toafamily ofalterna- tively spliced transcripts. Atleast twoGolli-MBP transcripts, containing thefirst three exons ofthegeneandoneormoreMBP exons, areproduced fromthefirst transcription start site. The second family oftranscripts contains onlyMBP exonsand produces thewell-known MBPs.Inhumans, RNAblot analysis revealed thatGolli-MBP transcripts wereexpressed infetal thymus, spleen, andhumanB-cell andmacrophage cell lines, as well asinfetal spinal cord. Thesermdings clearly linkthe expression ofexonsencoding theautoimmunogen/encephalito- genMBPinthecentral nervous system tocells andtissues ofthe immunesystem through normal expression oftheGolli-MBP gene. Theyalso establish that this genetic locus, which includes theMBP gene, isconserved amongspecies, providing further evidence that theMBP transcription unit isanintegral partof theGolli transcription unitandsuggest thatthis structural arrangement isimportant forthegenetic function and/or regulation ofthese genes. Themyelin basic protein (MBP)isapotent autoencephali- togenthatplays aroleinexperimental allergic encephalo- myelitis andpostvaccinal encephalomyelitis