While thou art pouring forth thy soul abroad
In such an ecstasy!
Still wouldst thou sing, and I have ears in vain…
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BIRD song was the inspiration for Keats’s Ode to a Nightingale – one can hardly imagine being similarly moved by a mouse’s squeak. Yet it seems that mice can sing, and that their songs to prospective mates are nearly as complex as those of birds. Their vocalisations are made at ultrasonic frequencies, which is why no one noticed them before, nor was ever moved to celebrate them in Romantic poetry.
Tim Holy and Zhongsheng Guo of Washington University School of Medicine in St Louis, Missouri, recorded the vocalisations of male mice when they were presented with female pheromones and found they were far more complex than expected. By digitally modifying the recorded vocalisations, they dropped the pitch by several octaves for analysis. The recordings included several syllable types that were arranged into phrases and motifs, fulfilling the definition of “song” (Public Library of Science Biology, DOI: 10.1371/journal.pbio.0030386). The calls of crickets and frogs, by contrast, are far simpler.
“The male mouse’s songs to prospective mates are ultrasonic, which is why no one had noticed them before”
Some bats sing in courtship, and whale song is well documented, but these were the only known mammalian songsmiths, apart from ourselves. So the fact that song has turned up in such a well-studied animal – the lab mouse – is all the more surprising.
What the songs are for is still uncertain, but since males are stimulated to sing when they smell female pheromones, it seems likely that singing serves to demonstrate their “quality” as a potential mate to females.
Singing in birds is used as a model system to investigate human speech and learning (see “Seeking the song genes”). But far more is known about mouse genetics and there are “mouse models” for many human diseases.
Holy hopes that studying the singing mouse will teach us fundamental principles about the brain, and help scientists understand communication disorders such as autism.
Seeking the Song Genes
If we knew how a bird’s genes allow it to learn to sing, we might understand better how we learn to speak. To do that research, though, we have to be able to manipulate birds genetically, and they have stubbornly resisted modification so far. But now it looks as though a relative of HIV could deliver foreign genes into bird cells.
Ben Scott and Carlos Lois at the Massachusetts Institute of Technology used a modified lentivirus to deliver a jellyfish gene into quail embryos. The gene codes for a protein that glows, so the researchers could check where it was expressed in the bird’s body.
Along with the jellyfish gene, the researchers also inserted a promoter sequence from the human synapsin gene. This switches on the gene next to it if it is in a nerve cell; in other cells the neighbouring gene stays off. Sure enough, in the genetically modified quails, it was only nerve cells that glowed green (Proceedings of the National Academy of Sciences, DOI: 10.1073/pnas.0508437102). But the technique is not yet as effective as in mice: only 30 to 40 per cent of bird cells become infected with the virus, compared with 90 per cent of mouse cells.
Lois thinks that transgenic birds could be used to investigate the genetic and neurobiological basis of learning and communication, because songbirds are important models for studying how we learn to speak. “The key here is that songbirds have a very sophisticated communication system that has to be learned, like humans,” says Lois.
He also foresees transgenic chickens that are resistant to diseases such as avian flu and tuberculosis.
