title: Cytoplasmic aggregates of dynactin in iPSC-derived tyrosine hydroxylase-positive neurons from a patient with Perry syndrome.
abstract: Perry syndrome is a rare autosomal dominant disorder clinically characterized by parkinsonism with depression/apathy, weight loss, and central hypoventilation. Eight mutations in DCTN1 gene have been reported. A novel disease model is required because the detailed pathogenesis remains unclear.
  
  
  
  To develop a novel model, we generated induced pluripotent stem cells (iPSCs) from a Perry syndrome patient with F52L mutation in DCTN1, and describe clinical and neuroimaging investigations. We differentiated iPSCs into tyrosine hydroxylase (TH)-positive neurons. Immunocytochemistry analyses of control and mutant were performed.
  
  
  
  The patient displayed levodopa responsive parkinsonism. Dopamine transporter single photon emission tomography showed markedly decreased uptake in the striatum, and metaiodobenzylguanidine cardiac scintigraphy also showed decreased uptake. Perry syndrome TH-positive neurons showed dynactin aggregates in cytoplasm.
  
  
  
  TH-positive neurons from Perry syndrome iPSCs recapitulated an aspect of the disease phenotype of Perry syndrome.
authors.affiliation: Center for iPS Cell Research and Application (CiRA), Kyoto University, 53 Kawahara-cho, Shogoin, Sakyo-ku, Kyoto, 606-8507, Japan; Department of Neurology, Fukuoka University School of Medicine, 7-45-1 Nanakuma, Jonan-ku, Fukuoka, 814-0180, Japan. Electronic address: mishima1006@fukuoka-u.ac.jp.
authors.forename: Takayasu
authors.initials: T
authors.lastname: Mishima
authors.affiliation: Center for iPS Cell Research and Application (CiRA), Kyoto University, 53 Kawahara-cho, Shogoin, Sakyo-ku, Kyoto, 606-8507, Japan; Sumitomo Dainippon Pharma, 3-1-98 Kasugadenaka, Konohana-ku, Osaka, 554-0022, Japan. Electronic address: taizo.ishikawa@cira.kyoto-u.ac.jp.
authors.forename: Taizo
authors.initials: T
authors.lastname: Ishikawa
authors.affiliation: Center for iPS Cell Research and Application (CiRA), Kyoto University, 53 Kawahara-cho, Shogoin, Sakyo-ku, Kyoto, 606-8507, Japan. Electronic address: keiko.imamura@cira.kyoto-u.ac.jp.
authors.forename: Keiko
authors.initials: K
authors.lastname: Imamura
authors.affiliation: Center for iPS Cell Research and Application (CiRA), Kyoto University, 53 Kawahara-cho, Shogoin, Sakyo-ku, Kyoto, 606-8507, Japan. Electronic address: takayuki.kondo@cira.kyoto-u.ac.jp.
authors.forename: Takayuki
authors.initials: T
authors.lastname: Kondo
authors.affiliation: Center for iPS Cell Research and Application (CiRA), Kyoto University, 53 Kawahara-cho, Shogoin, Sakyo-ku, Kyoto, 606-8507, Japan; Department of Neurology, Kyoto University Graduate School of Medicine, 54 Kawahara-cho, Shogoin, Sakyo-ku, Kyoto, 606-8507, Japan. Electronic address: ykoshiba@kuhp.kyoto-u.ac.jp.
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Koshiba
authors.affiliation: Department of Neurology, Kyoto University Graduate School of Medicine, 54 Kawahara-cho, Shogoin, Sakyo-ku, Kyoto, 606-8507, Japan. Electronic address: ryosuket@kuhp.kyoto-u.ac.jp.
authors.forename: Ryosuke
authors.initials: R
authors.lastname: Takahashi
authors.affiliation: Center for iPS Cell Research and Application (CiRA), Kyoto University, 53 Kawahara-cho, Shogoin, Sakyo-ku, Kyoto, 606-8507, Japan. Electronic address: jbtaka@cira.kyoto-u.ac.jp.
authors.forename: Jun
authors.initials: J
authors.lastname: Takahashi
authors.affiliation: Department of Neurology, National Omuta Hospital, 1044-1 Tachibana, Omuta, Fukuoka, 837-0911, Japan. Electronic address: watanabe-a@oomuta-h.com.
authors.forename: Akihiro
authors.initials: A
authors.lastname: Watanabe
authors.affiliation: Department of Neurology, National Omuta Hospital, 1044-1 Tachibana, Omuta, Fukuoka, 837-0911, Japan. Electronic address: fujii@oomuta.hosp.go.jp.
authors.forename: Naoki
authors.initials: N
authors.lastname: Fujii
authors.affiliation: Department of Neurology, Fukuoka University School of Medicine, 7-45-1 Nanakuma, Jonan-ku, Fukuoka, 814-0180, Japan. Electronic address: tsuboi@cis.fukuoka-u.ac.jp.
authors.forename: Yoshio
authors.initials: Y
authors.lastname: Tsuboi
authors.affiliation: Center for iPS Cell Research and Application (CiRA), Kyoto University, 53 Kawahara-cho, Shogoin, Sakyo-ku, Kyoto, 606-8507, Japan. Electronic address: haruhisa@cira.kyoto-u.ac.jp.
authors.forename: Haruhisa
authors.initials: H
authors.lastname: Inoue
mesh_terms: D003593:Cytoplasm / Q000378:metabolism*; D003863:Depression / Q000378:metabolism / Q000473:pathology; D000072159:Dynactin Complex / Q000378:metabolism*; D006801:Humans; D007040:Hypoventilation / Q000378:metabolism* / Q000473:pathology; D057026:Induced Pluripotent Stem Cells / Q000201:enzymology*; D008297:Male; D008869:Microtubule-Associated Proteins / Q000235:genetics*; D008875:Middle Aged; D009154:Mutation / Q000235:genetics; D009474:Neurons / Q000201:enzymology*; D020734:Parkinsonian Disorders / Q000378:metabolism* / Q000473:pathology; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism*; D057177:TDP-43 Proteinopathies
chemical_list: D000072159:Dynactin Complex; D008869:Microtubule-Associated Proteins; D014446:Tyrosine 3-Monooxygenase
keywords: Aggregate; DCTN1; Perry syndrome; Tyrosine hydroxylase-positive neuron; iPSC