Post Transcriptional Regulation of the Neurofibromatosis 2 Gene
Abstract
Neurofibromatosis type 2 (NF2) is associated with a homozygous inactivation of the neurofibromatosis 2 gene (NF2). Despite intense study of the NF2 gene, the mechanism by which the NF2 tumor suppressor acts to prevent tumor formation is not well understood. The NF2 transcripts undergo alternative splicing, generating a series of mRNA isoforms lacking one or more exons. Presently, the role of alternative splicing of NF2 mRNAs is not understood. The NF2 transcripts are also terminated at different polyadenylation sites. The role of this differential polyadenylation is not known. The goal of this research is to examine the role of posttranscriptional regulation (alternative splicing and differentiation polyadenylation) of the NF2 gene. During this reporting period, we have completed the analysis of the pattern and relative frequency of alternatively spliced NF2 isoforms expressed in vestibular schwannomas and various other human tissues and cells. We found that vestibular schwannomas express a distinct pattern of alternatively spliced NF2 transcripts lacking specific exons. We have produced transgenic mice carrying a 2.4-kb NF2 promoter-driven square-gal construct have been produced. Analysis of transgene expression showed that the 2.4-kb NF2 promoter could direct transgene expression to the nervous system during development. We also found that expression of the two schwannoma-expressed NF2 isoforms, lacking exons 15 and 16, or exons 8 and 16, respectively, did not affect the growth properties of 293 and RT4 cells. We are presently producing transgenic mice carrying the schwannoma-expressed NF2 cDNA isoforms driven by the human NF2 promoter or the mouse PO promoter to address whether these NF2 isoforms possess any properties conducive to tumor formation in vivo.
Document Details
- Document Type
- Technical Report
- Publication Date
- Aug 01, 2004
- Accession Number
- ADA428293
Entities
People
- Chang Long-sheng