Altered ultrasonic vocalization in mice with a disruption in the Foxp2 gene.
Neurobiology of speech and language has previously been studied in the KE family, in which half of the members have severe impairment in both speech and language. The gene responsible for the phenotype was mapped to chromosome 7q31 and identified as the FOXP2 gene, coding for a transcription factor containing a polyglutamine tract and a forkhead DNA-binding domain. Because of linkage studies implicating 7q31 in autism, where language impairment is a component of the disorder, and in specific language impairment, FOXP2 has also been considered as a potential susceptibility locus for the language deficits in autism and/or specific language impairment. In this study, we characterized mice with a disruption in the murine Foxp2 gene. Disruption of both copies of the Foxp2 gene caused severe motor impairment, premature death, and an absence of ultrasonic vocalizations that are elicited when pups are removed from their mothers. Disruption of a single copy of the gene led to modest developmental delay but a significant alteration in ultrasonic vocalization in response to such separation. Learning and memory appear normal in the heterozygous animals. Cerebellar abnormalities were observed in mice with disruptions in Foxp2, with Purkinje cells particularly affected. Our findings support a role for Foxp2 in cerebellar development and in a developmental process that subsumes social communication functions in diverse organisms.
Molecular Cardiology Research Center, Department of Medicine, University of Pennsylvania Medical Center, 956 Biomedical Research Building II/III, Philadelphia, PA 19104, USA.
Weiguo
W
Shu
Julie Y
JY
Cho
Yuhui
Y
Jiang
Minhua
M
Zhang
Donald
D
Weisz
Gregory A
GA
Elder
James
J
Schmeidler
Rita
R
De Gasperi
Miguel A Gama
MA
Sosa
Donald
D
Rabidou
Anthony C
AC
Santucci
Daniel
D
Perl
Edward
E
Morrisey
Joseph D
JD
Buxbaum
D000818:Animals; D015139:Blotting, Southern; D002525:Cerebellar Cortex / Q000002:abnormalities* / Q000473:pathology; D051858:Forkhead Transcription Factors; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D051379:Mice / Q000235:genetics* / Q000502:physiology; D011689:Purkinje Cells / Q000473:pathology; D012097:Repressor Proteins / Q000235:genetics*; D014465:Ultrasonics; D014828:Vocalization, Animal
D051858:Forkhead Transcription Factors; C432918:Foxp2 protein, mouse; D012097:Repressor Proteins