Cited by 233Genetics and Neurodevelopmental DisordersLanguage Development and DisordersAnimal Vocal Communication and Behavior

Ultrasonic vocalization impairment of Foxp2 (R552H) knockin mice related to speech-language disorder and abnormality of Purkinje cells

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Fujita, Eriko, Tanabe, Yuko, Shiota, Akira, Ueda, Masatsugu, Suwa, Kiyotaka, Momoi, Mariko Y., Momoi, Takashi·2008·Proceedings of the National Academy of Sciences

Abstract

Previous studies have demonstrated that mutation in the forkhead domain of the forkhead box P2 (FOXP2) protein (R553H) causes speech-language disorders. To further analyze FOXP2 function in speech learning, we generated a knockin (KI) mouse for Foxp2 (R552H) [Foxp2 (R552H)-KI], corresponding to the human FOXP2 (R553H) mutation, by homologous recombination. Homozygous Foxp2 (R552H)-KI mice showed reduced weight, immature development of the cerebellum with incompletely folded folia, Purkinje cells with poor dendritic arbors and less synaptophysin immunoreactivity, and achieved crisis stage for survival 3 weeks after birth. At postnatal day 10, these mice also showed severe ultrasonic vocalization (USV) and motor impairment, whereas the heterozygous Foxp2 (R552H)-KI mice exhibited modest impairments. Similar to the wild-type protein, Foxp2 (R552H) localized in the nuclei of the Purkinje cells and the thalamus, striatum, cortex, and hippocampus (CA1) neurons of the homozygous Foxp2 (R552H)-KI mice (postnatal day 10), and some of the neurons showed nuclear aggregates of Foxp2 (R552H). In addition to the immature development of the cerebellum, Foxp2 (R552H) nuclear aggregates may further compromise the function of the Purkinje cells and cerebral neurons of the homozygous mice, resulting in their death. In contrast, heterozygous Foxp2 (R552H)-KI mice, which showed modest impairment of USVs with different USV qualities and which did not exhibit nuclear aggregates, should provide insights into the common molecular mechanisms between the mouse USV and human speech learning and the relationship between the USV and motor neural systems.

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Crossref · 10.1073/pnas.0712298105

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  • The cortico-striatal circuitry mediates speech and language in humans.

    “These findings suggest that the cortico-striatal circuitry mediates speech and language in humans (Enard et al., 2009; Fujita et al., 2008; Schreiweis et al., 2014; Shu et al., 2005).”

    From Genetic Changes Shaping the Human Brain (2015) · cites this paper as Fujita et al., 2008

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Authors
Fujita, E., Tanabe, Y., Shiota, A., Ueda, M., Suwa, K., Momoi, M. Y., & Momoi, T.
Affiliations
  • National Institute of Neuroscience (JP)
  • PhoenixBio (Japan) (JP)
  • Jichi Medical University (JP)
Corresponding author
Momoi, Mariko Y.
Venue
Proceedings of the National Academy of Sciences
Published
2008-02-26
Volume
105
Issue
8
Pages
3117-3122
ISSN
  • 0027-8424 (ISSN-L)
  • 1091-6490
OpenAlex
W2085583998
Cited by
233
References
30
Citations by year
2026: 5 · 2025: 10 · 2024: 12 · 2023: 7 · 2022: 7 · 2021: 15 · 2020: 10 · 2019: 8 · 2018: 21 · 2017: 14 · 2016: 14 · 2015: 11 · 2014: 15 · 2013: 14 · 2012: 20
FWCI
9.50
Type
journal article
Language
en
Open access
Locations
  • Proceedings of the National Academy of Sciences (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Funders
Japan Society for the Promotion of Science (18700333, 19500305)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetics and Neurodevelopmental Disorders
  • Social Sciences › Psychology › Developmental and Educational Psychology › Language Development and Disorders
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Developmental Biology › Animal Vocal Communication and Behavior
Keywords
FOXP2, knock-in mice, ultrasonic vocalizations, speech and language disorders, Purkinje cells, cerebellar development, synaptophysin, nuclear aggregates, motor impairment, speech learning, heterozygous mice
MeSH terms
Animals, Cerebellum, Genotype, Histocytochemistry, Language Disorders, Mice, Transgenic, Purkinje Cells, Repressor Proteins, Ultrasonics, Vocalization, Animal, DNA Primers, Mutation, Missense, Microarray Analysis, Mice, Forkhead Transcription Factors

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