• Search Research Projects
  • Search Researchers
  • How to Use
  1. Back to previous page

Memory and learning disorder analysis using mutation mouse for mental retadation related gene ATRX and elucidation of the genetic control abnormality.

Research Project

Project/Area Number 15500210
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Neuroscience in general
Research InstitutionTOYAMA MEDICAL AND PHARMACEUTICAL UNIVERSITY

Principal Investigator

KITAJIMA Isao  Toyama Med Pharmaceut Univ., Lab Med., Professor, 医学部, 教授 (50214797)

Co-Investigator(Kenkyū-buntansha) NIHIJO Hisao  Toyama Med Pharmaceut Univ., Lab Med., Professor, 大学院・医学系研究科, 教授 (00189284)
Project Period (FY) 2003 – 2004
Project Status Completed (Fiscal Year 2004)
Budget Amount *help
¥3,700,000 (Direct Cost: ¥3,700,000)
Fiscal Year 2004: ¥1,600,000 (Direct Cost: ¥1,600,000)
Fiscal Year 2003: ¥2,100,000 (Direct Cost: ¥2,100,000)
KeywordsATRX syndrome / Knock out mouse / learning, behavior disorder / behavior analysis / cerebral cortex / hippocampus / cerebellum / Morris water maze / ATRX遺伝子 / ADHD / 記憶・学習障害 / プルキンエ細胞 / 精神遅滞 / 行動異常 / 多動症 / Morris水迷路試験 / Lac Z遺伝子
Research Abstract

The causative gene of the ATRX syndrome, which maps on chromosome X and shows such phenotypes as mental retardation and α thalassemia, is clarified. It has been reported that intelligence is lowered when exon 2 is mutated. Then, in cooperation with Dr.En Li and Dr.H.Beppu (Harvard University, USA), we performed back-crossing in the C57BL6 mouse system from the 129 mouse system to six generations (N6) in order to produce the ATRX mutant mouse for behavioral analysis. Using the C75BL6, N6 generation mouse, the following results were obtained over the two-year research period from 2003 to 2004. (1) The mutant mice have kock in highly Lac Z gene at the mutation site. The Lac Z gene was well observed in the hippocampus, cerebral cortex and cerebellum by X-gal staining. (2) Immunostaining was carried out with an antibody that recognized the C-terminus of ATRX. As a result, in comparison with the wild type, the low expression of the ATRX protein in the cerebral cortex, cerebellum, and hippoca … More mpus was recognized in the ATRX mutant mouse. (3) Using the antibody that recognized the C-terminus of ATRX, the mutant mouse showed decreased protein expression of approximately 50% in brain tissues by Western blot, in comparison with the wild type. (4) It is well known that the hippocampus controls memory and learning. Therefore, in order to analyze its function, we examined spatial memory learning with the Morris water maze test, and found that memory and learning capability of the mutant mouse were inferior to those of the wild type. This finding was confirmed in the diet remuneration test under the environment which removed aquaphobia. We also performed the open field test and the home cage activity test in order to examine other behavioral disorders of the mutant mouse. From these tests, we noted hyperactivity in the mutant mouse. Although it was affected by bright light in the wild type mouse, the sojourn time in the light-dark environment was reversed in the mutant mouse. The behavioral analysis revealed that the ATRX mutant mouse presented with low learning capability, photophobia sensitivity and hyperactivity. Less

Report

(3 results)
  • 2004 Annual Research Report   Final Research Report Summary
  • 2003 Annual Research Report
  • Research Products

    (29 results)

All 2005 2004 2003 Other

All Journal Article (20 results) Book (2 results) Publications (7 results)

  • [Journal Article] Pitavastatin at low dose activated endothelial nitric oxide synthase through P13K-Akt pathway in endothelial cells.2005

    • Author(s)
      Wang J, Tokoro T, Kitajima I, et al.
    • Journal Title

      Life Sciences 76(5)

      Pages: 2257-2268

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Analysis of molecular pathogenesis based on the view-Point of transcription factor, nuclear factor-kappa B : A plan for the transcriptional factor automational analysis Testing2005

    • Author(s)
      Kitajima I
    • Journal Title

      Jpn.J.C L A 30(1)

      Pages: 3-17

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Pitavastatin at low dose activates endothelial nitric Oxide synthase through PI3-AKT pathway in Endothelial cells.2005

    • Author(s)
      Wang J, Tokoro T, Matui K, Higa S, Kitajima I
    • Journal Title

      Life Sciences 76(19)

      Pages: 2257-2268

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Pitavasitatin at low dose activates endothelial nitric oxide synthase through PI3K-Akt pathway in endothelial cells.2005

    • Author(s)
      Wang J, Tokoro T, Kitajima I, et al.
    • Journal Title

      Life Sciences (In press)

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Mutation study of antithrombin : the role of disulfide bonds in the intracellular accumulation and formation of Russel body-like structures2005

    • Author(s)
      Tanaka Y, Ueda K, Kitajima I, et al.
    • Journal Title

      J.Biochem. (In press)

    • NAID

      10017343620

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Proof of the mysterious efficacy of ginseng : basic and clinical trials: effects of red ginseng on learning and memory deficits in animal model of amnesia.2004

    • Author(s)
      Nishijo H, Uwano T, Zhong YM, Ono T
    • Journal Title

      J.Pharmacol.Sci. 95(2)

      Pages: 145-152

    • NAID

      10013294615

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] シグナル伝達系異常と疾患2004

    • Author(s)
      北島 勲
    • Journal Title

      臨床化学 33(3,4)

      Pages: 163-176

    • NAID

      10014070678

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Annual Research Report 2004 Final Research Report Summary
  • [Journal Article] Proof of the mysterious efficacy of ginseng : basic and clinical trials : effects of red ginseng on learning and memory deficits in animal model of amnesia2004

    • Author(s)
      Nishijo H, Uwano T, Zhong YM, Ono T
    • Journal Title

      J.Pharmacol.Sci. 95(2)

      Pages: 145-152

    • NAID

      10013294615

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] BMP-Ilheterozygous mice have mild pulmonary Hypertension and impaired oulmonary vascular remodeling Response to prolong hypoxia.2004

    • Author(s)
      Beppu H, Ichose F, Kawai N et al.
    • Journal Title

      Am.J Physiol Lung Cell Mol Physiol 287

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Histone H3-K9 Methyltransferase ESET is essential for Early development.2004

    • Author(s)
      Dodge JE, Kang Y-K, Beppu H, et al.
    • Journal Title

      Mol.Cell.Biol 24(6)

      Pages: 2478-2486

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] The novel HMG-CoA reductase inhibitor, Pitavasitatin, induces a protective action in vascular endothelial cells through the production of nitric oxide (NO).2004

    • Author(s)
      Tokoro T, Wang J, Kitajima I
    • Journal Title

      Yakugaku Zasshi 124

      Pages: 121-126

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Proof of the mysterious efficacy of ginseng : basic and clinical trials : effects of red ginseng on learning and memory deficits in an animal model of amnesia2004

    • Author(s)
      NishijoH, Uwano T, Zhong YM, Ono T
    • Journal Title

      J.Pharmacol.Sci. 95(2)

      Pages: 145-152

    • NAID

      10013294615

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Differential activation in medical temporal lobe during a sound sequence discrimination task age in human subjects2004

    • Author(s)
      Takakura H, Umeno K, Nishijo H et al.
    • Journal Title

      Neuroscience 119(2)

      Pages: 517-532

    • Related Report
      2004 Annual Research Report
  • [Journal Article] ASK-1-p38MAPK/JNK signaling cascade mediates anandamide induced PC12 cell death.2003

    • Author(s)
      Sarker KP, Biswas KK, Yamakuchi M, Kitajima I, et al.
    • Journal Title

      J.Neurochem. 85(1)

      Pages: 50-61

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Induction of interleukin-8 monocyte chemoattractant protein-1 by Doxorubicin in human small cell cartinoma cells.2003

    • Author(s)
      Shibakura M, Niiya K, Kitajima I, et al.
    • Journal Title

      Int.J.Cancer 103

      Pages: 380-386

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Differential activation in medical temporal lobe during a sound sequence distrimination task age in human subjects.2003

    • Author(s)
      Takakura H, Umeno K, Nishijo H, et al.
    • Journal Title

      Neuroscience 119(2)

      Pages: 517-532

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] ASK-1-p38MAPK/JNK signaling cascade mediates anandamide induced PC12 cell death.2003

    • Author(s)
      Sarker KP, Biswas KK, Yamakuchi M, Kitajima I, et al.
    • Journal Title

      J.Neurochem 85(1)

      Pages: 50-61

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Representation of place by Monkey Hipocampal neuron In real and virtural translocation2003

    • Author(s)
      Hori E, Tabuchi E, Matsumura N, et al.
    • Journal Title

      Hippocampus 13

      Pages: 190-196

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] A method for accurate determination of stereotaxic Coordinates in single-unit recording studies in monkeys By high-resolution three-dimensional magnetic resonance Imaging.2003

    • Author(s)
      Akashi T, Tamura R, Eifuku S, et al.
    • Journal Title

      Neuroscience Research 47

      Pages: 255-260

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Differential activation in themedial temporal lobe during a sound-sequence discrimination task across age in human subjects2003

    • Author(s)
      Takakura H, Umeno K, Tabuchi E, et al.
    • Journal Title

      Neuroscience 119

      Pages: 517-532

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Book] モデル動物の作製と維持2004

    • Author(s)
      小澤哲夫, 北島 勲
    • Total Pages
      360
    • Publisher
      エル・アイ・シー
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Book] モデル動物の作製と維持2004

    • Author(s)
      小澤哲夫, 北島 勲
    • Total Pages
      360
    • Publisher
      エル、アイ、シー
    • Related Report
      2004 Annual Research Report
  • [Publications] Shibakura M, Niiya K, Kitajima I, et al.: "Induction of interleukin-8 and monocyte chemoattractant protein-1 by Doxorubicin in human small-cell lung cartinoma cells"Int.J.Cancer. 103. 380-386 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Sarker KP, BiswasKK, Yamakuchi M, Kitajima I, et al.: "ASK-1-p38MAPK/JNK signaling cascade mediates anandamide induced PC12 cell death"J.Neurochem.. 85(1). 50-61 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Arisato T, Sarker KP, Kitajima I, et al.: "The agonist of the protease-activated receptor-1 (PAR) but not PAR3 mimics thrombin-Induced vascular endothelial growth factor release in human smooth muscle cells"Cell.Mol.Life.Sci. 60(8). 1716-1724 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Sugimori K, Kawaguchi I, Kitajima I, et al.: "High-sensitive analysis of serum C-reactive protein in young patients with lumbar disc herniation"J.Bone Joint Surg.Br.. 85(8). 1151-1154 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Ogata N, Ichida T, Kitajima I, et al.: "Development of peptide nucleic acid mediated polymerase chain reaction clampimg (PMPC)"J.Jpn.Soc.Lab. Med.. 51. 313-319 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Ogata N, Takashima S, Kitajima I, et al.: "Antibody to hepatitis B surface antigen induced by recombinant hepatitis B vaccine consisting of subtype antigen is underestimated on WHO-standardized assay"Inter.Med.. 42(5). 446-447 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] 北島 勲(分担執筆): "医学書院医学大辞典(伊藤正男, 井村裕夫, 高久史麻 編)"医学書院. 3062 (2003)

    • Related Report
      2003 Annual Research Report

URL: 

Published: 2003-04-01   Modified: 2016-04-21  

Information User Guide FAQ News Terms of Use Attribution of KAKENHI

Powered by NII kakenhi