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A mouse model for human-specific changes in FOXP2, a gene important for speech and language.
Vortrag: Neuroscience Conference, 3-07 November 2007, San Diego, USA. (2007)
Comparisons of human and ape genomes generate hypotheses about the molecular basis of human-specific traits but the extent to which these hypotheses can be tested in experimental systems is currently unclear. One such hypothesis states that two human-specific amino acid changes encoded in the gene FOXP2 have been fixed by positive selection due to some effect on speech and language. We have generated a mouse model for these two amino acid changes and analyzed their effect on striatal gene expression, neuronal differentiation, electrophysiology, neuroanatomy, ultrasonic vocalizations of pups and over 240 other phenotypes. We find that the humanized FOXP2 has a significant effect on genome-wide gene expression patterns in the developing and adult striatum, leads to increased neurite outgrowth in differentiated neural precursors and increases the synaptic activity recorded from striatal medium spiny neurons. On a behavioral level, mice carrying the humanized FOXP2 explore a new environment more cautiously and vocalize at slightly lower frequencies and modulate calls differently. Our results indicate that human-specific amino acid changes in FOXP2 affected the brain and not other organs in which FOXP2 is also expressed. Furthermore, the changes in vocalization support the hypothesis that these changes affected speech and/or language while the neuronal phenotype suggests that the cellular mechanism by which this happened could have been increased neuronal connectivity. These findings open up new possibilities to study the neurological and molecular basis of human-specific properties of FOXP2 and allow guarded optimism that also other genetic changes that have been of importance during human evolution can be investigated using transgenic approaches in the mouse.
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Publication type Other: Lecture