title: Specific expression of FOXP2 in cerebellum improves ultrasonic vocalization in heterozygous but not in homozygous Foxp2 (R552H) knock-in pups.
abstract: The R553H mutation has been found in the FOXP2 gene of patients with speech-language disorder. Foxp2(R552H) knock-in (KI) mice exhibit poor dendritic development of Purkinje cells in the cerebellum and impaired ultrasonic vocalization (USV), which is related to human speech and language; compared with wild-type mice, heterozygous Foxp2(R552H)-KI pups exhibit the reduced number of whistle-type USVs and the increased short-type ones, while homozygous pups exhibit only click-type USVs but no whistle-type or short-type ones. To make clear the relationship between the role of Foxp2 in the cerebellum and whistle-type USVs activity, we prepared transgenic (Tg) mice specifically expressing human FOXP2-myc in cerebellum (Pcp2-FOXP2-myc-Tg mice) by using purkinje cell protein-2 (Pcp2) promoter. FOXP2-myc expression in the cerebellum increased the relative numbers of whistle-type USVs in the heterozygous Foxp2(R552H)-KI pups and recovered their USVs but did not in the homozygous ones. Foxp2 in the cerebellum may pertain to the brain network engaged in whistle-type USVs activities including modification, but not their production. There may be common molecular contribution of Purkinje cells to human FOXP2-mediated speech-language and mouse Foxp2-mediated USVs.
authors.affiliation: Center for Medical Science, International University, Kitakanemaru, Ohtawara 3248501, Tochigi, Japan; Department of Pediatrics, Jichi Medical University, Yakushiji, Shimotsukeshi 3290498, Tochigi, Japan.
authors.forename: Eriko
authors.initials: E
authors.lastname: Fujita-Jimbo
authors.affiliation: Center for Medical Science, International University, Kitakanemaru, Ohtawara 3248501, Tochigi, Japan. Electronic address: momoi@iuhw.ac.jp.
authors.forename: Takashi
authors.initials: T
authors.lastname: Momoi
mesh_terms: D000818:Animals; D002531:Cerebellum / Q000378:metabolism*; D051858:Forkhead Transcription Factors / Q000235:genetics / Q000378:metabolism*; D055879:Gene Knock-In Techniques; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D008822:Mice, Transgenic; D009419:Nerve Tissue Proteins / Q000235:genetics; D011689:Purkinje Cells / Q000378:metabolism; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism*; D014828:Vocalization, Animal
chemical_list: C465448:FOXP2 protein, human; D051858:Forkhead Transcription Factors; C432918:Foxp2 protein, mouse; D009419:Nerve Tissue Proteins; C091104:Purkinje cell protein L7; D012097:Repressor Proteins
keywords: Foxp2; Speech-language disorder; Ultrasonic vocalization