NEUROFIBROMATOSIS-1 (NF1) MESSENGER-RNAS EXPRESSED IN THE CENTRAL-NERVOUS-SYSTEM ARE DIFFERENTIALLY SPLICED IN THE 5' PART OF THE GENE

The neurofibromatosis 1 gene seems to play essential roles at several different stages of life, During embryogenesis, it is involved in card iac development while in the adult, neurofibromin (the corresponding p rotein) is mainly expressed in the nervous system, and therein, essent ially in neurons, non-myelinating Schwann cells and oligodendrocytes, In addition, the NF1 gene is considered a tumor suppressor gene, since mutations have been associated with the occurrence of benign and mali gnant tumors in neural-crest-derived tissues, Using reverse transcript ion-polymerase chain reaction (RT-PCR) analyses with primers located i n exons 7 and 13, we have identified evidence of alternative splicing in this region of the NF1 gene, Cloning and sequencing of cDNA allowed the characterization of an isoform bearing an extra 30 bp sequence be tween exons 9 and 10a, leading to the insertion of 10 amino acids betw een residues 420 and 421 of neurofibromin, The insertion is conserved in the mouse, Examination of the pattern of expression of this isoform demonstrated a high level of expression in the central nervous system and an absence of expression in all the other normal tissues tested i ncluding peripheral nervous tissues derived from the neural crest, Ana lysis of brain tumors indicated a reduced expression of the alternativ e exon in medulloblastomas and oligodendrogliomas. The results present ed here are consistent with tissue-specific expression of this alterna tive exon which we propose to call exon 9br.