title: Cntnap2 expression in the cerebellum of Foxp2(R552H) mice, with a mutation related to speech-language disorder.
abstract: Foxp2(R552H) knock-in (KI) mice carrying a mutation related to human speech-language disorder exhibit impaired ultrasonic vocalization and poor Purkinje cell development. Foxp2 is a forkhead domain-containing transcriptional repressor that associates with its co-repressor CtBP; Foxp2(R552H) displays reduced DNA binding activity. A genetic connection between FOXP2 and CNTNAP2 has been demonstrated in vitro, but not in vivo. Here we show that Cntnap2 mRNA levels significantly increased in the cerebellum of Foxp2(R552H) KI pups, although the cerebellar population of Foxp2-positive Purkinje cells was very small. Furthermore, Cntnap2 immunofluorescence did not decrease in the poorly developed Purkinje cells of Foxp2(R552H) KI pups, although synaptophysin immunofluorescence decreased. Cntnap2 and CtBP were ubiquitously expressed, while Foxp2 co-localized with CtBP only in Purkinje cells. Taken together, these observations suggest that Foxp2 may regulate ultrasonic vocalization by associating with CtBP in Purkinje cells; Cntnap2 may be a target of this co-repressor.
authors: Center for Medical Science, International University of Health and Welfare, 2600-1, Kitakanemaru, Ohtawara, Tochigi, Japan.
authors: Eriko
authors: E
authors: Fujita
authors: Yuko
authors: Y
authors: Tanabe
authors: Mariko Y
authors: MY
authors: Momoi
authors: Takashi
authors: T
authors: Momoi
mesh_terms: D000818:Animals; D001321:Autistic Disorder / Q000150:complications / Q000235:genetics / Q000378:metabolism; D002531:Cerebellum / Q000378:metabolism*; D056970:Co-Repressor Proteins; D004195:Disease Models, Animal; D005455:Fluorescent Antibody Technique; D051858:Forkhead Transcription Factors / Q000235:genetics*; D055879:Gene Knock-In Techniques; D007806:Language Disorders / Q000150:complications / Q000235:genetics* / Q000378:metabolism; D008297:Male; D008565:Membrane Proteins / Q000096:biosynthesis* / Q000235:genetics; D051379:Mice; D008817:Mice, Mutant Strains; D009154:Mutation; D009419:Nerve Tissue Proteins / Q000096:biosynthesis* / Q000235:genetics; D011689:Purkinje Cells / Q000378:metabolism; D012333:RNA, Messenger / Q000032:analysis; D012097:Repressor Proteins / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013064:Speech Disorders / Q000150:complications / Q000235:genetics* / Q000378:metabolism
chemical_list: C568163:CNTNAP2 protein, mouse; D056970:Co-Repressor Proteins; D051858:Forkhead Transcription Factors; C432918:Foxp2 protein, mouse; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; D012333:RNA, Messenger; D012097:Repressor Proteins