Aberrant processing of the Fugu HD (FrHD) mRNA in mouse cells and in transgenic mice
| Autor: | Kirupa Sathasivam, Hans Lehrach, Fabien Bertaux, Ichiro Kanazawa, Laura Mangiarini, Sarah Baxendale, Colin Hetherington, Gillian P. Bates |
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| Rok vydání: | 1997 |
| Předmět: |
Huntingtin
Mice Transgenic Nerve Tissue Proteins Biology Takifugu Genome Cell Line Mice Genetics Huntingtin Protein Animals RNA Messenger RNA Processing Post-Transcriptional Promoter Regions Genetic Molecular Biology Gene Genetics (clinical) Fugu fungi Nuclear Proteins General Medicine biology.organism_classification Huntington Disease Regulatory sequence Human genome Fishes Poisonous |
| Zdroj: | Human molecular genetics. 6(12) |
| ISSN: | 0964-6906 |
| Popis: | The puffer fish ( Fugu rubripes ) has a compact genome of 400 Mbp which is approximately 7.5-fold smaller than the human genome. It contains a similar number of genes but is deficient in intergenic, intronic and dispersed repetitive sequences. Fugu is becoming established as the model vertebrate genome for the identification and characterisation of novel human genes and conserved regulatory sequences. It has also been proposed that Fugu genes may provide natural mini-genes for the production of transgenic mice. We have used the Fugu homologue of the Huntington's disease (HD) gene to test this possibility. The human and Fugu HD genes cover 170 kb and 23 kb respectively and have previously been sequenced in their entirety. In Fugu tissue, the Fugu HD gene was found to be expressed as predicted from the gene sequence but three differentially spliced forms were also detected. Despite the absence of conserved promoter sequences, the Fugu promoter was found to be functional in mouse cells. We have generated mice transgenic for the Fugu HD gene and conducted a detailed expression analysis across the entire 10 kb transcript. This revealed the presence of many aberrant splice forms which would be incompatible with the production of the Fugu huntingtin protein. The Fugu HD gene is incorrectly processed in mouse cells both in vitro and in vivo which sheds doubt on the usefulness of Fugu genes for transgenesis. |
| Databáze: | OpenAIRE |
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