PuSH - Publikationsserver des Helmholtz Zentrums München

Export: TXT Text RIS Endnote (RIS) BIB BibTeX
Enard, W.* ; Hammerschmidt, K.* ; Brückner, M.K.* ; Giger, T.* ; Gehre, S.* ; Hölter, S.M. ; Becker, L. ; Groszer, M.* ; Wiebe, V.* ; Nickel, B.* ; Müller, U.* ; Adler, T. ; Bolle, I.* ; Busch, D.H. ; Calzada-Wack, J. ; Dalke, C. ; Ehrhardt, N. ; Favor, J. ; Fuchs, H. ; Gailus-Durner, V. ; Hans, W. ; Hölzlwimmer, G.* ; Javaheri, A.* ; Kling, E. ; Kunder, S.* ; Moßbrugger, I.* ; Rácz, I. ; Rathkolb, B. ; Rozman, J. ; Schrewe, A. ; Graw, J. ; Hrabě de Angelis, M. ; Ivandic, B. ; Kalaydjiev, S.* ; Klingenspor, M. ; Klopstock, T. ; Ollert, M. ; Quintanilla-Martinez, L.* ; Schulz, H. ; Wolf, E. ; Wurst, W. ; Zimmer, A. ; Fisher, S.E.* ; Arendt, T.* ; Fischer, J.* ; Schwarz, J.* ; Pääbo, S.*

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.
Tags
Anmerkungen
Besondere Publikation
Auf Hompepage verbergern

Zusatzinfos bearbeiten
Eigene Tags bearbeiten
Privat
Eigene Anmerkung bearbeiten
Privat
Auf Publikationslisten für
Homepage nicht anzeigen
Als besondere Publikation
markieren
Publikationstyp Sonstiges: Vortrag
Sprache englisch
Veröffentlichungsjahr 2007
HGF-Berichtsjahr 0
Konferenztitel Neuroscience Conference
Konferzenzdatum 3-07 November 2007
Konferenzort San Diego, USA
Institut(e) Institute of Developmental Genetics (IDG)
Institute of Experimental Genetics (IEG)
Institute of Pathology (PATH)
Institute of Lung Health and Immunity (LHI)
Institute of Human Genetics (IHG)
POF Topic(s) 30204 - Cell Programming and Repair
30201 - Metabolic Health
30504 - Mechanisms of Genetic and Environmental Influences on Health and Disease
Forschungsfeld(er) Genetics and Epidemiology
Enabling and Novel Technologies
PSP-Element(e) G-500500-001
G-500600-001
G-500300-001
G-500500-002
G-500600-003
Erfassungsdatum 2007-12-31
[➜Korrektur melden]