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.
Shu
Weiguo
W
Molecular Cardiology Research Center, Department of Medicine, University of Pennsylvania Medical Center, 956 Biomedical Research Building II/III, Philadelphia, PA 19104, USA.
Cho
Julie Y
JY
Jiang
Yuhui
Y
Zhang
Minhua
M
Weisz
Donald
D
Elder
Gregory A
GA
Schmeidler
James
J
De Gasperi
Rita
R
Sosa
Miguel A Gama
MA
Rabidou
Donald
D
Santucci
Anthony C
AC
Perl
Daniel
D
Morrisey
Edward
E
Buxbaum
Joseph D
JD
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