2003 Fiscal Year Annual Research Report

Rett症候群の動物モデルにおける分子基盤の確立と遺伝子治療に関する研究

Research Project

Project/Area Number	14370255
Research Institution	Kurume University
Principal Investigator	松石豊次郎久留米大学, 医学部, 教授 (60157237)
Co-Investigator(Kenkyū-buntansha)	小戝健一郎久留米大学, 高次脳疾患研究所, 教授 (90258418) 古賀靖敏久留米大学, 医学部, 助教授 (00225400) 山下裕史朗久留米大学, 医学部, 講師 (90211630) 高嶋幸男国際医療福祉大学, 大学院, 教授 (70038743) 近藤郁子愛媛大学, 医学部・衛生学, 教授 (20110489)
Keywords	Rett症候群 / Methyl-CpG-binding protein2 / モデル動物 / 遺伝子治療 / 再生医学
Research Abstract	ヒトおよびモデル動物のRett症候群(RTT)で、臨床症状と遺伝子変異部位との関係性を研究した。 Methyl-CpG-binding protein 2(MECP2)の変異は検索した219名中145名の患者さんで約66%のRTTの患者さんに認められ、45の変異が見つかった。T158M変異は最もcommonな変異で22名(19.1%)に見られ、以下順にR168X(14.8%)、R270X(13%)、R255X(9.6%)、R29X(6.1%)であった。 R133Cは軽症で有意味語を持つpreserved speech variantに多くみられた。RTT患者では脳脊髄液(CSF)のβ-フニルエチラミンが低下していた。RTT患者の脳を用いた神経病理学的検索ではチロシン水酸化酵素の免疫染色性は青斑核で低下し、トリプトフアン水酸化酵素は縫線核で低下、サブスタンスP、メチオニンエンケファリンも著明に低下し呼吸障害、自律神経症状との関連が考えられた。現在Methyl-CpG-binding protein 2(MECP2)-null mutationモデル動物をJackson Laboratoryから購入し、X^-/Y(ヘミの雄)は発症し、呼吸異常、下肢のclaspingを認めている。またメスのヘテロX^-/Xも神経症状を発現している。現在、脳病理組織を保存し、コントロールマウスと比較検討中である。現在遺伝子治療も開始しMECP2遺伝子を発現するアデノウイルスベクター(Ad.CMV-MECP2)は既に作成し、またマウスのES細胞からの神経細胞分化誘導係においてMECP2遺伝子の役割、分子機能を分子生物学的手法で解析中であり興味あるデータが集積されつつある。

Research Products

(12 results)

All Other

All Publications (12 results)

[Publications] Wada N,...Matsuishi T: "Pyruvate Dehydrogenase Ela subunit deficiency in a female patient : evidence of antenatal origin of brain damage and possinle etiology of infantile spasms."Brain Development. 26. 57-60 (2004)
[Publications] Yamashita Y,.....Matsuishi T: "Possible association between congenitall cytomegalovirus infection and autistic disorder"Journal of Autism and Developmental Disorder. 33. 455-459 (2003)
[Publications] Fukui R,...Matsuishi T, Nishi A: "Effect of methylphenidate on dopamine/DARPP signallyng in adult, but not young mice"Journal of Neurochemistry. 87. 1391-1401 (2003)
[Publications] Egami K,...Matsuishi T, Imaizumi T: "Role of host angiotensin II type 1 receptor in tumor angiogenesis and growth."Jornal of Clinical Investigation. 112. 67-75 (2003)
[Publications] 松石豊次郎: "Rett症候群"小児内科. 35・増刊号. 804-807 (2003)
[Publications] Leonard H,...Matsuishi T, Yamashita Y: "Patients with the R133C mutation : Is their phenotype different from patients with Rett syndrome with ther mutation?"Journal of Medical Genetics. 40. 1-7 (2003)
[Publications] Tsuneoka M..., Kosai K..., Yamamoto A: "C-myc induces autophagy in rat 3Y1 fibroblast cells"Cell Structure and Function. 28. 195-204 (2003)
[Publications] Terazaki Y,...Kosai K: "An optimal therapeutic expression level is crucial for suicide gene therapy for hepatic metastatic cancer in mice"Hepatology. 37. 155-163 (2003)
[Publications] Li Y,...Kosai K,...Fujiwara H: "Postinfarction treatment with an adenovirus vector expressing hepatocyte growth factor relieves chronic left ventricular remodeling and dysfunction in mice"Circulation. 107. 2499-2506 (2003)
[Publications] Nagano S,...Kosai K: "Gene therapy eradicationg, distant disseminated micro metastases by optimal cytokine expression in the primary lesion only : Novel concepts for uccessful cytokine gene therapy."International Journal of Oncology. 24. 549-558 (2004)
[Publications] Ikoma T,...Kosai K: "A definitive role of RhoC in metastasis of orthotopic lung cancer in mice"Clinical Cancer Research. 10. 1192-1200 (2004)
[Publications] Hirayama A,...Takashima S: "Myelin transcription factor 1(MyT1)immuneoreactivity in infants with perivetricular Leukomalacia"Developmental Brain Reseach. 140. 85 (2003)

2003 Fiscal Year Annual Research Report

Rett症候群の動物モデルにおける分子基盤の確立と遺伝子治療に関する研究

Principal Investigator

松石 豊次郎 久留米大学, 医学部, 教授 (60157237)

Research Products

[Publications] Wada N,...Matsuishi T: "Pyruvate Dehydrogenase Ela subunit deficiency in a female patient : evidence of antenatal origin of brain damage and possinle etiology of infantile spasms."Brain Development. 26. 57-60 (2004)

[Publications] Yamashita Y,.....Matsuishi T: "Possible association between congenitall cytomegalovirus infection and autistic disorder"Journal of Autism and Developmental Disorder. 33. 455-459 (2003)

[Publications] Fukui R,...Matsuishi T, Nishi A: "Effect of methylphenidate on dopamine/DARPP signallyng in adult, but not young mice"Journal of Neurochemistry. 87. 1391-1401 (2003)

[Publications] Egami K,...Matsuishi T, Imaizumi T: "Role of host angiotensin II type 1 receptor in tumor angiogenesis and growth."Jornal of Clinical Investigation. 112. 67-75 (2003)

[Publications] 松石豊次郎: "Rett症候群"小児内科. 35・増刊号. 804-807 (2003)

[Publications] Leonard H,...Matsuishi T, Yamashita Y: "Patients with the R133C mutation : Is their phenotype different from patients with Rett syndrome with ther mutation?"Journal of Medical Genetics. 40. 1-7 (2003)

[Publications] Tsuneoka M..., Kosai K..., Yamamoto A: "C-myc induces autophagy in rat 3Y1 fibroblast cells"Cell Structure and Function. 28. 195-204 (2003)

[Publications] Terazaki Y,...Kosai K: "An optimal therapeutic expression level is crucial for suicide gene therapy for hepatic metastatic cancer in mice"Hepatology. 37. 155-163 (2003)

[Publications] Li Y,...Kosai K,...Fujiwara H: "Postinfarction treatment with an adenovirus vector expressing hepatocyte growth factor relieves chronic left ventricular remodeling and dysfunction in mice"Circulation. 107. 2499-2506 (2003)

[Publications] Nagano S,...Kosai K: "Gene therapy eradicationg, distant disseminated micro metastases by optimal cytokine expression in the primary lesion only : Novel concepts for uccessful cytokine gene therapy."International Journal of Oncology. 24. 549-558 (2004)

[Publications] Ikoma T,...Kosai K: "A definitive role of RhoC in metastasis of orthotopic lung cancer in mice"Clinical Cancer Research. 10. 1192-1200 (2004)

[Publications] Hirayama A,...Takashima S: "Myelin transcription factor 1(MyT1)immuneoreactivity in infants with perivetricular Leukomalacia"Developmental Brain Reseach. 140. 85 (2003)

松石豊次郎久留米大学, 医学部, 教授 (60157237)