Human Molecular Genetics, Vol 6, 2141-2149, Copyright © 1997 by Oxford University Press
K Sathasivam, S Baxendale, L Mangiarini, F Bertaux, C Hetherington, I Kanazawa, H Lehrach and GP Bates
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.
ARTICLES
Aberrant processing of the Fugu HD (FrHD) mRNA in mouse cells and in transgenic mice
Division of Medical and Molecular Genetics, UMDS, Guy's Hospital, London SE1 9RT, UK.
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