"Long before it's in the papers"
September 14, 2014


Smarter mice with a “humanized” gene?

Sept. 15, 2014
Courtesy of PNAS
and World Science staff

In­tro­duc­ing a “hu­man­ized” ver­sion of a lan­guage-linked gene in­to mice ac­cel­er­ates their learn­ing, ac­cord­ing to a stu­dy.

The gene, called Foxp2, is of a type known as tran­scrip­tion fac­tor—a gene that con­trols the ac­ti­vity of oth­er genes. It has al­so been linked to the de­vel­op­ment of hu­man speech and lan­guage. The gene is found in both hu­mans and mice, in slightly dif­fer­ent forms.

In the new stu­dy, re­search­ers cre­at­ed mice whose ver­sion of the Foxp2 gene had changes in two key ami­no acids—some­what equiv­a­lent to two “let­ters” of its ge­net­ic code. The changes were de­signed to make the gene more si­m­i­lar to hu­man Foxp2.

The study aimed at learn­ing “how ge­net­ic changes might have adapted the nerv­ous sys­tem” to lan­guage and speech, wrote the sci­en­tists, Ann Gray­biel of the Mas­sa­chu­setts In­sti­tute of Tech­nol­o­gy and col­leagues. The re­port ap­peared Sept. 15 on­line in the jour­nal Pro­ceed­ings of the Na­t­ional Acad­e­my of Sci­ences.

The re­port, how­ev­er, did­n't ad­dress what some sci­en­tists have de­scribed as eth­i­cal ques­tions posed by the mix­ing of hu­man and an­i­mal genes. One con­cern, for ex­am­ple, is that hu­man­ity might even­tu­ally have to con­front the weighty is­sue of wheth­er an an­i­mal with some hu­man genes de­serves hu­man rights.

Gray­biel and col­leagues found that the two-“letter” change af­fect­ed a part of the mouse brain known as the stria­tum and re­lat­ed cir­cuits called the cortico-basal gan­glia. These ar­eas are “known to be es­sen­tial for mo­tor and cog­ni­tive be­hav­iors such as speech and lan­guage ca­pa­bil­i­ties in hu­mans,” ex­plained a sum­mary of the re­port is­sued by the jour­nal.

Dif­fer­ent por­tions of the stria­tum un­der­lie two modes of learn­ing con­sid­ered cru­cial for speech and lan­guage, the re­search­ers said. One is a con­scious form of learn­ing called de­clar­a­tive learn­ing; the oth­er, a non-con­scious form called pro­ce­du­ral learn­ing. 

In a se­ries of maze ex­pe­ri­ments, mice with the “hu­man­ized” gene learn­ed stimulus-response as­socia­t­ions more rap­idly than reg­u­lar mice when both de­clar­a­tive and pro­ce­du­ral forms of learn­ing were en­gaged, the in­ves­ti­ga­tors re­ported.

Parts of the stria­tum as­sociated with these two modes of learn­ing were found to re­spond dif­fer­ently in the mice, as judged by lev­els of dopamine, a mes­sen­ger chem­i­cal in the brain; by gene ac­ti­vity pat­terns; and by change­abil­ity in the strength of brain con­nec­tions, known as syn­ap­tic plas­ti­city. The find­ings sug­gest that the hu­manized gene dif­fer­ently in­flu­ences how dif­fer­ent re­gions of the stria­tum con­trib­ute to learn­ing, said the re­search­ers, who spec­u­late that these ef­fects may have con­trib­uted to the emer­gence of hu­man lan­guage.

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Introducing a “humanized“ version of a language-linked gene into mice accelerates their learning, according to a study. The gene, called Foxp2, is of a type known as transcription factor—a gene that controls the activity of other genes. It has also been linked to the development of human speech and language. The gene is found in both humans and mice, in slightly different forms. In the new study, researchers created mice whose version of the Foxp2 gene had changes in two amino acids, somewhat equivalent to two “letters“ of its genetic code. The changes were designed to make the gene more similar to human Foxp2. The study aimed at learning “how genetic changes might have adapted the nervous system“ to language and speech, wrote the scientists, Ann Graybiel of the Massachusetts Institute of Technology and colleagues. The report appeared Sept. 15 online in the journal Proceedings of the National Academy of Sciences. The report, however, didn't address what some scientists have described as ethical issues posed by the mixing of human and animal genes. One concern, for example, is that humanity might eventually have to confront the weighty issue of whether an animal with some human genes deserves human rights. Graybiel and colleagues found that the two-“letter“ change affected a part of the mouse brain known as the striatum and related circuits called the cortico-basal ganglia. These areas are “known to be essential for motor and cognitive behaviors such as speech and language capabilities in humans,“ explained a summary of the report issued by the journal. Different portions of the striatum underlie two modes of learning considered crucial for speech and language, the researchers said. One is a conscious form of learning called declarative learning; the other, a non-conscious form called procedural learning. In a series of navigational maze experiments, mice with the “humanized“ gene learned stimulus-response associations more rapidly than regular mice when both declarative and procedural forms of learning were engaged, the investigators reported. Parts of the striatum associated with these two modes of learning were found to respond differently in the mice, as judged by levels of dopamine, a messenger chemical in the brain; by gene activity patterns; and by changeability in the strength of brain connections, known as synaptic plasticity. The findings suggest that the humanized gene differently influences how different regions of the striatum contribute to learning, said the researchers, who speculate that these effects may have contributed to the emergence of human language.