A Human Language Gene Changes the Sound of Mouse Squeaks

By NICHOLAS WADE

People have a deep desire to communicate with animals, as is evident from the way they converse with their dogs, enjoy myths about talking animals or devote lifetimes to teaching chimpanzees how to speak. A delicate, if tiny, step has now been taken toward the real thing: the creation of a mouse with a human gene for language.

The gene, FOXP2, was identified in 1998 as the cause of a subtle speech defect in a large London family, half of whose members have difficulties with articulation and grammar. All those affected inherited a disrupted version of the gene from one parent. FOXP2 quickly attracted the attention of evolutionary biologists because other animals also possess the gene, and the human version differs significantly in its DNA sequence from those of mice and chimpanzees, just as might be expected for a gene sculpted by natural selection to play an important role in language.

Researchers at the Max Planck Institute for Evolutionary Anthropology in Leipzig, Germany, have now genetically engineered a strain of mice whose FOXP2 gene has been swapped out for the human version. Svante Paabo, in whose laboratory the mouse was engineered, promised several years ago that when the project was completed, “We will speak to the mouse.” He did not promise that the mouse would say anything in reply, doubtless because a great many genes must have undergone evolutionary change to endow people with the faculty of language, and the new mouse was gaining only one of them. So it is perhaps surprising that possession of the human version of FOXP2 does in fact change the sounds that mice use to communicate with other mice, as well as other aspects of brain function.

That is the result reported in the current issue of the journal Cell by Wolfgang Enard, also of the Leipzig institute, and a large team of German researchers who studied 300 features of the humanized mice. FOXP2, a gene whose protein product switches on other genes, is important during the embryo’s development and plays an active part in constructing many tissues, including the lungs, stomach and brain. The gene is so vital that mice in which both copies of the gene are disrupted die after a few weeks.

Despite the mammalian body’s dependence on having its two FOXP2 genes work just right, Dr. Enard’s team found that the human version of FOXP2 seemed to substitute perfectly for the mouse version in all the mouse’s tissues except for the brain.

In a region of the brain called the basal ganglia, known in people to be involved in language, the humanized mice grew nerve cells that had a more complex structure. Baby mice utter ultrasonic whistles when removed from their mothers. The humanized baby mice, when isolated, made whistles that had a slightly lower pitch, among other differences, Dr. Enard says. Dr. Enard argues that putting significant human genes into mice is the only feasible way of exploring the essential differences between people and chimps, our closest living relatives.

There are about 20 million DNA differences between the genomes of humans and chimps, but most make no physical difference. To understand which DNA changes are important, the genes must be put into another species. There is no good way of genetically engineering chimps, even it were ethically acceptable, so the mouse is the test of choice, in Dr. Enard’s view.

Dr. Joseph Buxbaum, an expert on the molecular basis of psychiatric disease at Mount Sinai Medical Center, said Dr. Enard’s team had taken a good first step toward understanding the role of FOXP2 in the development of the brain. “The most surprising finding, and cause for great optimism, is that the gene does seem to have a great effect on pathways of neural development in mice,” he said.

Dr. Gary Marcus, who studies language acquisition at New York University, said the study showed lots of small effects from the human FOXP2, which fit with the view that FOXP2 plays a vital role in language, probably with many other genes that remain to be discovered. “People shouldn’t think of this as the one language gene but as part of a broader cascade of genes,” he said. “It would have been truly spectacular if they had wound up with a talking mouse.”