title: Human mutant huntingtin disrupts vocal learning in transgenic songbirds.
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.
authors.affiliation: Laboratory of Animal Behavior, The Rockefeller University, New York, New York, USA.
authors.forename: Wan-Chun
authors.initials: WC
authors.lastname: Liu
authors.affiliation: Laboratory of Animal Behavior, The Rockefeller University, New York, New York, USA.
authors.forename: Jessica
authors.initials: J
authors.lastname: Kohn
authors.affiliation: Laboratory of Animal Behavior, The Rockefeller University, New York, New York, USA.
authors.forename: Sarah K
authors.initials: SK
authors.lastname: Szwed
authors.affiliation: Laboratory of Animal Behavior, The Rockefeller University, New York, New York, USA.
authors.forename: Eben
authors.initials: E
authors.lastname: Pariser
authors.affiliation: Laboratory of Animal Behavior, The Rockefeller University, New York, New York, USA.
authors.forename: Sharon
authors.initials: S
authors.lastname: Sepe
authors.affiliation: Laboratory of Animal Behavior, The Rockefeller University, New York, New York, USA.
authors.forename: Bhagwattie
authors.initials: B
authors.lastname: Haripal
authors.affiliation: Laboratory of Mammalian Cell Biology and Development, The Rockefeller University, New York, New York, USA.
authors.forename: Naoki
authors.initials: N
authors.lastname: Oshimori
authors.affiliation: Neurodegeneration Laboratory, University of California, San Diego, La Jolla, California, USA.
authors.forename: Martin
authors.initials: M
authors.lastname: Marsala
authors.affiliation: Vector Development Core Lab, UCSD School of Medicine, La Jolla, California, USA.
authors.forename: Atsushi
authors.initials: A
authors.lastname: Miyanohara
authors.affiliation: CHDI Management Inc., New York, New York, USA.
authors.forename: Ramee
authors.initials: R
authors.lastname: Lee
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified; D001479:Basal Ganglia / Q000502:physiology; D046369:Finches; D006801:Humans; D000071058:Huntingtin Protein; D007858:Learning / Q000502:physiology*; D009419:Nerve Tissue Proteins / Q000235:genetics*; D009474:Neurons / Q000502:physiology*; D020308:Songbirds / Q000502:physiology; D014828:Vocalization, Animal / Q000502:physiology*
chemical_list: C086055:HTT protein, human; D000071058:Huntingtin Protein; D009419:Nerve Tissue Proteins