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Foxp2 – Speech and language in mice and men

The human FOXP2 gene is known to be important for the acquisition of speech and language as well as in speech and language disorders. Analyses of the evolution of the FOXP2 gene in primates identified two amino acid substitutions, which became fixed on the human lineage after its separation from the chimpanzee and which appear to have been subject to positive selection, probably due to effects on some aspects of speech and language. The mouse Foxp2 protein differs from the chimpanzee version only in one amino acid which makes the mouse an ideal model for the ancestral situation before the separation of the human lineage from chimpanzees.

The scientists around Wolfgang Enard established a mouse model where only the two varying amino acids between mice and men were substituted. Thus this mouse is carrying a human version of Foxp2 (Foxp2hum) which should make it possible to study the functional consequences of the evolutionary changes that affected the transcription factor FOXP2 in humans.

To identify the physiological systems that might be affected by the amino acid substitutions mouse mutants were analyzed in the German Mouse Clinic (GMC). Although the mutants seem to be generally healthy the comprehensive phenotypic analysis revealed qualitatively different ultrasonic vocalizations, decreased exploratory behavior and decreased dopamine concentrations in the brain suggesting that the humanized Foxp2 allele affects basal ganglia.

In contrast to wildtype littermates, the mutant mice traveled shorter distances at a lower mean velocity, made fewer turns and were in general more anxious and reserved. To relate the results of these mice to a loss of function of Foxp2, knockout mice were also screened in the GMC. Foxp2wt/ko mice showed decreased hearing ability and worse motoric learning, had a higher amount of fat mass and a lower amount of lean mass, ate more food and showed changes in certain blood parameters.

Taken together Foxp2hum leads to variation of sound generation in the mouse. Results from the phenotypic screening support the hypothesis that the two amino acid substitutions that occurred during human evolution affect aspects of speech and/or language.

 

A humanized version of Foxp2 affects cortico-basal ganglia cirbuits in mice“, Enard et al., Cell 137, 961-971