title: Cadm1-expressing synapses on Purkinje cell dendrites are involved in mouse ultrasonic vocalization activity.
abstract: Foxp2(R552H) knock-in (KI) mouse pups with a mutation related to human speech-language disorders exhibit poor development of cerebellar Purkinje cells and impaired ultrasonic vocalization (USV), a communication tool for mother-offspring interactions. Thus, human speech and mouse USV appear to have a Foxp2-mediated common molecular basis in the cerebellum. Mutations in the gene encoding the synaptic adhesion molecule CADM1 (RA175/Necl2/SynCAM1/Cadm1) have been identified in people with autism spectrum disorder (ASD) who have impaired speech and language. In the present study, we show that both Cadm1-deficient knockout (KO) pups and Foxp2(R552H) KI pups exhibit impaired USV and smaller cerebellums. Cadm1 was preferentially localized to the apical-distal portion of the dendritic arbor of Purkinje cells in the molecular layer of wild-type pups, and VGluT1 level decreased in the cerebellum of Cadm1 KO mice. In addition, we detected reduced immunoreactivity of Cadm1 and VGluT1 on the poorly developed dendritic arbor of Purkinje cells in the Foxp2(R552H) KI pups. However, Cadm1 mRNA expression was not altered in the Foxp2(R552H) KI pups. These results suggest that although the Foxp2 transcription factor does not target Cadm1, Cadm1 at the synapses of Purkinje cells and parallel fibers is necessary for USV function. The loss of Cadm1-expressing synapses on the dendrites of Purkinje cells may be associated with the USV impairment that Cadm1 KO and Foxp2(R552H) KI mice exhibit.
authors.affiliation: Center for Medical Science, International University of Health and Welfare, Kitakanemaru, Ohtawara, Tochigi, Japan.
authors.forename: Eriko
authors.initials: E
authors.lastname: Fujita
authors.forename: Yuko
authors.initials: Y
authors.lastname: Tanabe
authors.forename: Beat A
authors.initials: BA
authors.lastname: Imhof
authors.forename: Mariko Y
authors.initials: MY
authors.lastname: Momoi
authors.forename: Takashi
authors.initials: T
authors.lastname: Momoi
mesh_terms: D000818:Animals; D000075982:Cell Adhesion Molecule-1; D015815:Cell Adhesion Molecules / Q000235:genetics / Q000378:metabolism*; D002531:Cerebellum / Q000002:abnormalities / Q000378:metabolism; D002648:Child; D002659:Child Development Disorders, Pervasive / Q000235:genetics; D003712:Dendrites / Q000235:genetics / Q000378:metabolism*; D005260:Female; D051858:Forkhead Transcription Factors / Q000235:genetics / Q000378:metabolism; D005838:Genotype; D006801:Humans; D015151:Immunoblotting; D007136:Immunoglobulins / Q000235:genetics / Q000378:metabolism*; D007150:Immunohistochemistry; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D009154:Mutation; D011689:Purkinje Cells / Q000378:metabolism*; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013064:Speech Disorders / Q000235:genetics; D013569:Synapses / Q000378:metabolism*; D014465:Ultrasonics; D050598:Vesicular Glutamate Transport Protein 1 / Q000378:metabolism; D014828:Vocalization, Animal
chemical_list: C498598:Cadm1 protein, mouse; D000075982:Cell Adhesion Molecule-1; D015815:Cell Adhesion Molecules; D051858:Forkhead Transcription Factors; C432918:Foxp2 protein, mouse; D007136:Immunoglobulins; D012097:Repressor Proteins; C493465:Slc17a7 protein, mouse; D050598:Vesicular Glutamate Transport Protein 1