Takayasu Mishima1, Taizo Ishikawa2, Keiko Imamura3, Takayuki Kondo4, Yasushi Koshiba5, Ryosuke Takahashi6, Jun Takahashi7, Akihiro Watanabe8, Naoki Fujii9, Yoshio Tsuboi10, Haruhisa Inoue11. 1. 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. 2. 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. 3. 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. 4. 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. 5. 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. 6. 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. 7. 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. 8. Department of Neurology, National Omuta Hospital, 1044-1 Tachibana, Omuta, Fukuoka, 837-0911, Japan. Electronic address: watanabe-a@oomuta-h.com. 9. Department of Neurology, National Omuta Hospital, 1044-1 Tachibana, Omuta, Fukuoka, 837-0911, Japan. Electronic address: fujii@oomuta.hosp.go.jp. 10. 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. 11. 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.
Abstract
BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: TH-positive neurons from Perry syndrome iPSCs recapitulated an aspect of the disease phenotype of Perry syndrome.
BACKGROUND: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. METHODS: To develop a novel model, we generated induced pluripotent stem cells (iPSCs) from a Perry syndromepatient 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. RESULTS: 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. CONCLUSIONS: TH-positive neurons from Perry syndrome iPSCs recapitulated an aspect of the disease phenotype of Perry syndrome.