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“Language gene” alters mouse squeaks

May 28, 2009
Courtesy Cell Press
and World Science staff

Mice car­ry­ing a “hu­man­ized” ver­sion of a gene be­lieved to in­flu­ence speech and lan­guage may not ac­tu­ally talk, but none­the­less have a lot to say about our ev­o­lu­tion­ary past, a new study suggests.

Mice car­ry­ing a “hu­man­ized ver­sion” of a gene be­lieved to in­flu­ence speech and lan­guage may not ac­tu­ally talk, but none­the­less have a lot to say about our ev­o­lu­tion­ary past, a new study suggests. (Im­age cour­tesy Berk­e­ley Nat'l Lab)
The al­tered mice show changes in brain cir­cuits pre­vi­ously tied to hu­man speech, re­search­ers  found. In­tri­guing­ly, they said, the mod­i­fied mouse pups al­so have dif­fer­ences in the high-pitched squeaks they use when moved out­side their moth­ers’ nests. But no one knows what the changes mean.

The findings are reported in the May 29 is­sue of the re­search jour­nal Cell.

“In the last dec­ade or so, we’ve come to real­ize that the mouse is really si­m­i­lar to hu­mans,” said Wolf­gang Enard of the Max Planck In­sti­tute for Ev­o­lu­tion­ary An­thro­po­l­ogy in Leip­zig, Ger­ma­ny, lead auth­or of the re­port. “The genes are es­sen­tially the same and they al­so work sim­i­larly.” Be­cause of that, sci­en­tists have learn­ed much about hu­man dis­eases by stu­dy­ing mice. 

“With this stu­dy, we get the first glimpse that mice can be used to study not only dis­ease, but al­so our own his­to­ry.” 

Enard said his team is gen­er­ally in­ter­est­ed in the ge­no­mic dif­fer­ences that set hu­mans apart from their pri­mate rel­a­tives. One im­por­tant dif­fer­ence be­tween hu­mans and chim­panzees they have stud­ied are two changes in “let­ters” of ge­net­ic code in a gene called FOXP2. Those changes be­came en­trenched in hu­mans af­ter our split from chim­panzees. “Changes in FOXP2 oc­curred over the course of hu­man ev­o­lu­tion and are the best can­di­dates for ge­net­ic changes that might ex­plain why we can speak,” Enard said. 

The re­search­ers in­tro­duced those sub­sti­tu­tions in­to the FOXP2 gene of mice. They said the mouse ver­sion of the gene is es­sen­tially iden­ti­cal to that of chimps, mak­ing it a rea­son­a­ble mod­el for the an­ces­tral hu­man ver­sion. Al­though FoxP2 is ac­tive in many oth­er tis­sues of the body, the al­tered ver­sion did not ap­pear to have oth­er ef­fects on the mice, which ap­peared to be healthy. 

The dif­fer­ences of­fer a win­dow in­to the ev­o­lu­tion of speech and lan­guage ca­pacity in the hu­man brain, ac­cord­ing to the sci­en­tists. They said it will now be im­por­tant to fur­ther ex­plore the ba­sis of the gene’s ef­fects and their pos­si­ble rela­t­ion­ship to char­ac­ter­is­tics that dif­fer be­tween hu­mans and apes. 

“Cur­rently, one can only spec­u­late about the role these ef­fects may have played dur­ing hu­man ev­o­lu­tion,” the in­ves­ti­ga­tors wrote. “How­ever, since pa­tients that car­ry one non­func­tion­al FOXP2 al­lele [cop­y] show im­pair­ments in the tim­ing and se­quenc­ing of oro­fa­cial move­ments,” one pos­si­bil­ity is that the changes in FOXP2 “con­tributed to an in­creased fine-tuning of mo­tor con­trol nec­es­sary for ar­ticula­t­ion.”

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Mice carrying a “humanized version” of a gene believed to influence speech and language may not actually talk, but they nonetheless have a lot to say about our evolutionary past, according to a report in the May 29 issue of the research journal Cell. The altered mice show changes in brain circuits previously tied to human speech, the new research found. Intriguingly, the modified mouse pups also have differences in the high-pitched squeaks they use when moved outside their mothers’ nests, according to researchers. But no one knows what the changes mean. “In the last decade or so, we’ve come to realize that the mouse is really similar to humans,” said Wolfgang Enard of the Max-Planck Institute for Evolutionary Anthropology in Leipzig, Germany. “The genes are essentially the same and they also work similarly.” Because of that, scientists have learned a tremendous amount about the biology of human diseases by studying mice. “With this study, we get the first glimpse that mice can be used to study not only disease, but also our own history.” Enard said his team is generally interested in the genomic differences that set humans apart from their primate relatives. One important difference between humans and chimpanzees they have studied are two changes in “letters” of genetic code in a gene called FOXP2. Those changes became entrenched in humans after our split from chimpanzees. “Changes in FOXP2 occurred over the course of human evolution and are the best candidates for genetic changes that might explain why we can speak,” Enard said. The researchers introduced those substitutions into the FOXP2 gene of mice. They said the mouse version of the gene is essentially identical to that of chimps, making it a reasonable model for the ancestral human version. Although FoxP2 is active in many other tissues of the body, the altered version did not appear to have other effects on the mice, which appeared to be healthy. The differences offer a window into the evolution of speech and language capacity in the human brain, according to the scientists. They said it will now be important to further explore the basis of the gene’s effects and their possible relationship to characteristics that differ between humans and apes. “Currently, one can only speculate about the role these effects may have played during human evolution,” the investigators wrote. “However, since patients that carry one nonfunctional FOXP2 allele [copy] show impairments in the timing and sequencing of orofacial movements,” one possibility is that the changes in FOXP2 “contributed to an increased fine-tuning of motor control necessary for articulation.”