Making Fish Genes Work in Human Cells

Findings on Fugu gene splicing could help scientists develop pufferfish transgenes for mammalian cells, say researchers at Massachusetts Institute of Technology.

Nov 22, 2004
Cathy Holding
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Courtesy of Mike Sexton

Findings on Fugu gene splicing could help scientists develop pufferfish transgenes for mammalian cells, say researchers at Massachusetts Institute of Technology. The Fugu genome contains all the alternative promoters and splice exons and introns present in mammalian genomes, but because the introns are so much smaller, genes are about an eighth the size, says MIT's Christopher Burge. This makes the Fugu genome a potentially powerful tool for functional gene analysis, he says, but scientists have until now been frustrated in their attempts to use them because mammalian cells do not correctly splice the fish genes.

By comparing human, mouse, zebrafish, and Fugu genomes, Burge's group discovered that intronic splicing enhancers appear to differ substantially between mammals and fish.1 By applying a scoring method to individual intron sequences, says Burge, Fugu genes can be tested for problem motifs and modified for transgenic experiments in mice – a method he has successfully piloted. "You have to do a bit of extra cloning or site-directed mutagenesis," he says, "but these Fugu genes would be much easier to manipulate and that much more genetically tractable."

"I think the paper's of interest in terms of understanding the potential of regulation and some of the details of the mechanisms of splicing," says James Manley at Columbia University. "I think these sequences will stand up and really be important elements."