Human mutant huntingtin disrupts vocal learning in transgenic songbirds

Wan Chun Liu, Jessica Kohn, Sarah K. Szwed, Eben Pariser, Sharon Sepe, Bhagwattie Haripal, Naoki Oshimori, Martin Marsala, Atsushi Miyanohara, Ramee Lee

Research output: Contribution to journalArticle

13 Scopus citations

Abstract

Speech and vocal impairments characterize many neurological disorders. However, the neurogenetic mechanisms of these disorders are not well understood, and current animal models do not have the necessary circuitry to recapitulate vocal learning deficits. We developed germline transgenic songbirds, zebra finches (Taneiopygia guttata) expressing human mutant huntingtin (mHTT), a protein responsible for the progressive deterioration of motor and cognitive function in Huntington's disease (HD). Although generally healthy, the mutant songbirds had severe vocal disorders, including poor vocal imitation, stuttering, and progressive syntax and syllable degradation. Their song abnormalities were associated with HD-related neuropathology and dysfunction of the cortical-basal ganglia (CBG) song circuit. These transgenics are, to the best of our knowledge, the first experimentally created, functional mutant songbirds. Their progressive and quantifiable vocal disorder, combined with circuit dysfunction in the CBG song system, offers a model for genetic manipulation and the development of therapeutic strategies for CBG-related vocal and motor disorders.

Original languageEnglish (US)
Pages (from-to)1617-1622
Number of pages6
JournalNature Neuroscience
Volume18
Issue number11
DOIs
StatePublished - Nov 1 2015

ASJC Scopus subject areas

  • Neuroscience(all)

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    Liu, W. C., Kohn, J., Szwed, S. K., Pariser, E., Sepe, S., Haripal, B., Oshimori, N., Marsala, M., Miyanohara, A., & Lee, R. (2015). Human mutant huntingtin disrupts vocal learning in transgenic songbirds. Nature Neuroscience, 18(11), 1617-1622. https://doi.org/10.1038/nn.4133