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.
journal_name
Nat Neuroscijournal_title
Nature neuroscienceauthors
Liu WC,Kohn J,Szwed SK,Pariser E,Sepe S,Haripal B,Oshimori N,Marsala M,Miyanohara A,Lee Rdoi
10.1038/nn.4133subject
Has Abstractpub_date
2015-11-01 00:00:00pages
1617-22issue
11eissn
1097-6256issn
1546-1726pii
nn.4133journal_volume
18pub_type
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