| Autor: |
Serena Altilia, Livia Pisciotta, Rita Garuti, Patrizia Tarugi, Alfredo Cantafora, Laura Calabresi, Jacopo Tagliabue, Sergio Maccari, Franco Bernini, Ilaria Zanotti, Carlo Vergani, Stefano Bertolini, Sebastiano Calandra |
| Jazyk: |
angličtina |
| Rok vydání: |
2003 |
| Předmět: |
|
| Zdroj: |
Journal of Lipid Research, Vol 44, Iss 2, Pp 254-264 (2003) |
| Druh dokumentu: |
article |
| ISSN: |
0022-2275 |
| DOI: |
10.1194/jlr.M200248-JLR200 |
| Popis: |
Two point mutations of ABCA1 gene were found in a patient with Tangier disease (TD): i) G>C in intron 2 (IVS2 +5G>C) and ii) c.844 C>T in exon 9 (R282X). The IVS2 +5G>C mutation was also found in the brother of another deceased TD patient, but not in 78 controls and 33 subjects with low HDL. The IVS2 +5G>C mutation disrupts ABCA1 pre-mRNA splicing in fibroblasts, leading to three abnormal mRNAs: devoid of exon 2 (Ex2−/mRNA), exon 4 (Ex4−/mRNA), or both these exons (Ex2−/Ex4−/mRNA), each containing a translation initiation site. These mRNAs are expected either not to be translated or generate short peptides. To investigate the in vitro effect of IVS2 +5G>C mutation, we constructed two ABCA1 minigenes encompassing Ex1–Ex3 region, one with wild-type (WTgene) and the other with mutant (MTgene) intron 2. These minigenes were transfected into COS1 and NIH3T3, two cell lines with a different ABCA1 gene expression. In COS1 cells, WTgene pre-mRNA was spliced correctly, while the splicing of MTgene pre-mRNA resulted in Ex2−/mRNA. In NIH3T3, no splicing of MTgene pre-mRNA was observed, whereas WTgene pre-mRNA was spliced correctly.These results stress the complexity of ABCA1 pre-mRNA splicing in the presence of splice site mutations. |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
|
