An alternatively-spliced mRNA in the carboxy terminus of the neurofibromatosis type 1 (NF1) gene is expressed in muscle

The gene for neurofibromatosis type 1 (NF1) was identified bypositional cloning and found to contain two alternatively splicedexons. The first described alternatively spliced exon (exon23a) is located within the GAP-related domain of the gene andinserts an additional 63 nucleotides into the NF1 mRNA. Thesecond alternatively spliced exon (exon 48a) is located nearthe extreme carboxy terminus of the gene and inserts an additional54 nucleotides into the mRNA. This second isoform, termed 3'ALT,was originally detected while screening a fetal brain cDNA library.Examination of its expression by reverse-transcribed RNA PCRdemonstrates high level of expression in cardiac muscle, skeletalmuscle and smooth muscle. Trace levels of expression are detectedin brain and nerve. The 3'ALT isoform is expressed in fetalcardiac muscle, adult left ventricle and cardiac Purkinje cells.Further confirmation of the existence of this isoform was obtainedby blotting the PCR products with a radiolabeled oligonucleotideentirely derived from sequences contained within exon 48a andby direct sequencing of the PCR products. Additionally, thisisoform is expressed in muscle tissues from other vertebratespecies. The expression of this isoform in muscle suggests thatthe NF1 gene may play additional tissue-specific roles in muscledevelopment and signal transduction.