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The elucidation of pathogenesis of developmental disorders induced by maternal nutritional condition in the fetal stage.

Research Project

Project/Area Number 23240062
Research Category

Grant-in-Aid for Scientific Research (A)

Allocation TypeSingle-year Grants
Section一般
Research Field Laboratory animal science
Research InstitutionThe Institute of Physical and Chemical Research

Principal Investigator

WAKANA Shigeharu  独立行政法人理化学研究所, バイオリソースセンター, チームリーダー (90192434)

Co-Investigator(Kenkyū-buntansha) KUBOTA Takeo  山梨大学, 医学工学総合研究部, 教授 (70293511)
FURUICHI Teiichi  東京理科大学, 理工学部応用生物学科, 教授 (50219094)
Project Period (FY) 2011-05-31 – 2014-03-31
Project Status Completed (Fiscal Year 2013)
Budget Amount *help
¥49,400,000 (Direct Cost: ¥38,000,000、Indirect Cost: ¥11,400,000)
Fiscal Year 2013: ¥12,350,000 (Direct Cost: ¥9,500,000、Indirect Cost: ¥2,850,000)
Fiscal Year 2012: ¥15,210,000 (Direct Cost: ¥11,700,000、Indirect Cost: ¥3,510,000)
Fiscal Year 2011: ¥21,840,000 (Direct Cost: ¥16,800,000、Indirect Cost: ¥5,040,000)
KeywordsDOHaD / 発達障害 / 行動解析 / 実験動物学 / 胎児期栄養 / CAPSタンパク質 / 葉酸 / 遺伝子発現 / マウス / 胎生妊娠期低栄養 / エピジェネティクス / 発達障害モデル / エピゲノム / モデルマウス
Research Abstract

The Developmental Origins of Health and Disease:DOHaD paradigm is a concept that in utero experiences reprogram an individual for later-in-life risk of diseases. In this study, we conducted experiments to validate the DOHaD theory in the developmental disorder with well-controlled experimental procedures using mouse model. We provided AIN93G as control diet and low-protein diet (LP) to pre-pregnant and pregnant females. After birth, behavioral phenotypes of offspring, gene expression level in brain, and genomic methylation levels in promoters of genes were examined. The offspring which were exposed to malnutrition in utero exhibited increased activity in the home cage, decreased contact to novel object, and decreased social investigation. The adult offspring of LP group group exhibited different pattern of mRNA expression and genomic methylation pattern relative to AIN93G group. However, no direct interaction between expression levels and methylation levels of genes were detected.

Report

(4 results)
  • 2013 Annual Research Report   Final Research Report ( PDF )
  • 2012 Annual Research Report
  • 2011 Annual Research Report
  • Research Products

    (42 results)

All 2014 2013 2012 2011 Other

All Journal Article (13 results) (of which Peer Reviewed: 9 results) Presentation (27 results) (of which Invited: 4 results) Book (2 results)

  • [Journal Article] マウス胎児期低栄養モデルを用いたDOHaD 仮説の検証2014

    • Author(s)
      古瀬民生, 若菜茂晴
    • Journal Title

      精神科

      Volume: 24 Pages: 335-339

    • Related Report
      2013 Final Research Report
  • [Journal Article] 発達障害とエピジェネティクス-環境と遺伝子をつなぐ新しい見方2014

    • Author(s)
      久保田健夫
    • Journal Title

      発達障害の進歩

      Volume: 26 Pages: 61-67

    • Related Report
      2013 Annual Research Report 2013 Final Research Report
  • [Journal Article] マウス胎児期低栄養モデルを用いたDOHaD仮説の検証2014

    • Author(s)
      古瀬民生・若菜茂晴
    • Journal Title

      精神科

      Volume: 24 Pages: 335-339

    • Related Report
      2013 Annual Research Report
  • [Journal Article] Pheno-Pub: a total support system for the publication of mouse phenotypic data on the web2013

    • Author(s)
      Suzuki T, Furuse T, Yamada I, Motegi H, Kozawa Y, Masuya H, Wakana S.
    • Journal Title

      Mamm. Genome

      Volume: 24 Issue: 11-12 Pages: 473-483

    • DOI

      10.1007/s00335-013-9482-y

    • Related Report
      2013 Annual Research Report 2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] CAPS1 deficiency perturbs dense-core vesicle trafficking and Golgi structure and reduces presynaptic release probability in the mouse brain.2013

    • Author(s)
      Sadakata T, Kakegawa W, Shinoda Y, Hosono M, Katoh-Semba R, Sekine Y, Sato Y, Tanaka M, Iwasato T, Itohara S, Furuyama K, Kawaguchi Y, Ishizaki Y, Yuzaki M, Furuichi T.
    • Journal Title

      J Neurosci.

      Volume: 33 Issue: 44 Pages: 17326-17334

    • DOI

      10.1523/jneurosci.2777-13.2013

    • Related Report
      2013 Annual Research Report 2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Autistic-like behavioral phenotypes in a mouse model with copy number variation of the CAPS2/CADPS2 gene2013

    • Author(s)
      Sadakata T, Shinoda Y, Oka M, Sekine Y, Furuichi T.
    • Journal Title

      FEBS Lett

      Volume: 587 Issue: 1 Pages: 54-59

    • DOI

      10.1016/j.febslet.2012.10.047

    • Related Report
      2013 Annual Research Report 2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Mouse models of mutations and variations in autism spectrum disorder-associated genes : mice expressing caps2/cadps2 copy number and alternative splicing variants2013

    • Author(s)
      Sadakata T, Shinoda Y, Sato A, Iguchi H, Ishii C, Matsuo M, Yamaga R, Furuichi T
    • Journal Title

      Int J Environ Res Public Health

      Volume: 10 Issue: 12 Pages: 6335-6353

    • DOI

      10.3390/ijerph10126335

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Animal Models of Autism Spectrum Disorder (ASD): A Synaptic-Level Approach to Autistic-Like Behavior in Mice2013

    • Author(s)
      Shinoda Y, Sadakata T, Furuichi T
    • Journal Title

      Experimental Animals

      Volume: 62 Issue: 2 Pages: 71-78

    • DOI

      10.1538/expanim.62.71

    • NAID

      10031163545

    • ISSN
      0007-5124, 1341-1357, 1881-7122
    • Related Report
      2013 Annual Research Report 2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] E pigenetics in neurodevelopmental an d mental disorders2013

    • Author(s)
      Kubota T, Miyake K, Hirasawa T
    • Journal Title

      Med Epigenet

      Volume: 1 Pages: 61-67

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] The role of epigenetics in Rett sydro me2013

    • Author(s)
      Kubota T, Miyake K, Hirasawa T
    • Journal Title

      Epigenomics

      Volume: 5 Issue: 5 Pages: 583-592

    • DOI

      10.2217/epi.13.54

    • Related Report
      2013 Annual Research Report 2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Comparison of genomic and epigenomic expression in monozygotic twins discordant for Rett syndrome2013

    • Author(s)
      Miyake K, Yang C, Minakuchi Y, Ohori K, Soutome M, Hirasawa T, Kazuki Y, Adachi N, Suzuki S, Itoh M, Goto Y, Andoh T, Kurosawa H, Akamatsu W, Oyama M, Okano H, Oshimura M, Sasaki M, Toyoda A, Kubota T
    • Journal Title

      PLoS ONE

      Volume: 8 Issue: 6 Pages: e66729-e66729

    • DOI

      10.1371/journal.pone.0066729

    • Related Report
      2013 Annual Research Report 2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] 特集 メタボリックシンドロームと周産期管理(DOHaDを含む)「 DOHaD 仮説とエピジェネティクス」2012

    • Author(s)
      久保田健夫
    • Journal Title

      周産期医学

      Volume: 42 Pages: 837-840

    • Related Report
      2013 Final Research Report
  • [Journal Article] Behavioral and neuromorphological characterization of a novel Tuba1 mutant mouse2012

    • Author(s)
      Furuse T., Yamada I., Kushida T., Masuya H., Ikuo Miura., Kaneda H., Kobayashi K., Wada Y.,Yuasa S., Wakana S
    • Journal Title

      Behavioral Brain Research

      Volume: 227 Issue: 1 Pages: 167-174

    • DOI

      10.1016/j.bbr.2011.11.002

    • Related Report
      2013 Final Research Report 2011 Annual Research Report
    • Peer Reviewed
  • [Presentation] The effects of maternal malnutrition in utero on behavioral phenotypes of mouse-validation of DOHaD theory in mouse2013

    • Author(s)
      Furuse T, Yamada I, Kaneda H, Kobayashi K, Kohda T, Ishino F, Miyake K, Kubota T, Wakana S
    • Organizer
      The 27th International Mammalian Genome Conference
    • Place of Presentation
      Salamanca, Spain
    • Year and Date
      2013-09-17
    • Related Report
      2013 Final Research Report
  • [Presentation] マウスモデルを用いたDOHaD 仮説の評価 : 母体低栄養が産仔の行動表現に与える影響2013

    • Author(s)
      古瀬民生
    • Organizer
      包括脳科学研究推進支援ネットワーク夏のワークショップ
    • Place of Presentation
      名古屋国際会議場(名古屋市)
    • Year and Date
      2013-08-31
    • Related Report
      2013 Final Research Report
  • [Presentation] マウス胎児期低栄養曝露された新生仔の遺伝子発現と表現型解析2013

    • Author(s)
      若菜茂晴, 古瀬民生
    • Organizer
      第40回日本毒性学会学術年会
    • Place of Presentation
      幕張メッセ(千葉市)
    • Year and Date
      2013-06-19
    • Related Report
      2013 Final Research Report
  • [Presentation] マウス胎生期低栄養モデルからの知見2013

    • Author(s)
      古瀬民生, 若菜茂晴
    • Organizer
      第2回日本DOHaD 研究会年会
    • Place of Presentation
      厚生労働省戸山研究庁舎(新宿区)
    • Year and Date
      2013-06-07
    • Related Report
      2013 Final Research Report
  • [Presentation] マウスモデルを用いたDOHaD 仮説の実証2 : 母体低栄養が新生仔の行動表現型に与える影響2013

    • Author(s)
      古瀬民生, 幸田尚, 串田知子, 柏村実生, 山田郁子, 金田秀貴, 小林喜美男, 石野史敏, 古市貞一, 久保田健夫, 若菜茂晴
    • Organizer
      第60回日本実験動物学会総会
    • Place of Presentation
      つくば国際会議場(つくば市)
    • Year and Date
      2013-05-15
    • Related Report
      2013 Final Research Report
  • [Presentation] The effects of maternal malnutrition in utero on behavioral phenotypes of mouse–validation of DOHaD theory in mouse2013

    • Author(s)
      Furuse T, Yamada I, Kaneda H, Kobayashi K, Kohda T, Ishino F, Miyake K, Kubota T, Wakana S.
    • Organizer
      The 27th International Mammalian Genome Conference
    • Place of Presentation
      Salamanca, Spain
    • Related Report
      2013 Annual Research Report
  • [Presentation] マウスを用いたDOHaD仮説検証実験計画-I -胎児期低栄養曝露された新生仔の遺伝子発現-2013

    • Author(s)
      若菜茂晴
    • Organizer
      第83回日本衛生学会学術総会:シンポジウム 出生前から生涯にわたる健康を守るための概念DOHaDの実証研究
    • Place of Presentation
      金沢市:金沢大学鶴間キャンパス
    • Related Report
      2012 Annual Research Report
    • Invited
  • [Presentation] マウスモデルを用いたDOHaD 仮説の実証 : 遺伝子発現パターンからみた胎生期低栄養の影響の脳-肝臓間差異2012

    • Author(s)
      古瀬民生, 幸田尚, 山田郁子, 三浦郁生, 金田秀貴, 小林喜美男, 石野史敏, 久保田健夫, 若菜茂晴
    • Organizer
      第35回日本神経科学大会
    • Place of Presentation
      名古屋国際会議場(名古屋市)
    • Year and Date
      2012-09-21
    • Related Report
      2013 Final Research Report
  • [Presentation] マウスモデルを用いたDOHaD 仮説の検証その1 : 母体低栄養が新生児の出生体重と遺伝子発現に与える影響2012

    • Author(s)
      古瀬民生, 幸田尚, 串田知子, 山田郁子, 金田秀貴, 小林喜美男, 石野史敏, 久保田健夫, 若菜茂晴
    • Organizer
      第26回モロシヌス研究会
    • Place of Presentation
      東京大学(東京都)
    • Year and Date
      2012-06-15
    • Related Report
      2013 Final Research Report
  • [Presentation] マウスモデルを用いたDOHaD 仮説の実証1 : 母体低栄養が新生児の出生体重と遺伝子発現に与える影響2012

    • Author(s)
      古瀬民生、幸田尚、串田知子、山田郁子、尾崎藍、金田秀貴、石野史敏、久保田健夫、若菜茂晴
    • Organizer
      日本実験動物科学・技術九州2012
    • Place of Presentation
      別府コンベンションセンター(別府市)
    • Year and Date
      2012-05-24
    • Related Report
      2013 Final Research Report
  • [Presentation] マウスを用いたDOHaD検証計画‐胎児期低栄養曝露された新生仔の遺伝子発現‐2012

    • Author(s)
      若菜茂晴, 古瀬民生, 幸田尚, 古市貞一, 三宅邦夫, 久保田健夫
    • Organizer
      第83回日本衛生学会学術総会
    • Place of Presentation
      金沢大学(金沢市)
    • Year and Date
      2012-03-25
    • Related Report
      2013 Final Research Report
  • [Presentation] マウスモデルを用いたDOHaD仮説の検証1:母体低栄養が新生仔の出生体重と遺伝子発現に与える影響2012

    • Author(s)
      古瀬民生
    • Organizer
      第59回日本実験動物学会総会
    • Place of Presentation
      別府市:別府市国際コンベンションセンター
    • Related Report
      2012 Annual Research Report
  • [Presentation] マウスモデルを用いたDOHaD仮説の検証1:母体低栄養が新生仔の出生体重と遺伝子発現に与える影響2012

    • Author(s)
      古瀬民生
    • Organizer
      第26回モロシヌス研究会
    • Place of Presentation
      東京都 東京大学農学部
    • Related Report
      2012 Annual Research Report
  • [Presentation] マウスモデルを用いたDOHaD仮説の実証:遺伝子発現パターンからみた胎生期栄養の影響の脳ー肝臓間の差異2012

    • Author(s)
      古瀬民生
    • Organizer
      第35回日本神経科学学会
    • Place of Presentation
      名古屋市:名古屋国際会議場
    • Related Report
      2012 Annual Research Report
  • [Presentation] Overview of the high throughput phenotyping program and pipelines in the Japan Mouse Clinic and its role in IMPC2011

    • Author(s)
      Wakana S
    • Organizer
      Rodent Pathology in Translational Research and Phenotyping Workshop
    • Place of Presentation
      Taipei, Taiwan
    • Year and Date
      2011-10-17
    • Related Report
      2013 Final Research Report
    • Invited
  • [Presentation] Introduction of mouse models for human psychiatric diseases in RIKEN ENU mutagenesis program2011

    • Author(s)
      Furuse T
    • Organizer
      Rodent Pathology in Translational Research and Phenotyping Workshop
    • Place of Presentation
      Taipei, Taiwan
    • Year and Date
      2011-10-17
    • Related Report
      2013 Final Research Report
    • Invited
  • [Presentation] Overview of the high throughput phenotyping program and pipelines in the Japan Mouse Clinic and its role in IMPC2011

    • Author(s)
      Shigeharu Wakana
    • Organizer
      Rodent Pathology in Translational Research and Phenotyping Workshop
    • Place of Presentation
      Taipei, Taiwan(招待講演)
    • Year and Date
      2011-10-17
    • Related Report
      2011 Annual Research Report
  • [Presentation] Introduction of mouse models for human psychiatric diseases in RIKENENU mutagenesis program2011

    • Author(s)
      Tamio Furuse
    • Organizer
      Rodent Pathology in Translational Research and Phenotyping Workshop
    • Place of Presentation
      Taipei, Taiwan(招待講演)
    • Year and Date
      2011-10-17
    • Related Report
      2011 Annual Research Report
  • [Presentation] IMPC 参加に向けた各表現型解析センター間における行動表現型のデータ変換と比較2011

    • Author(s)
      古瀬民生, 他6名
    • Organizer
      第34回日本神経科学大会
    • Place of Presentation
      パシフィコ横浜(横浜市)
    • Year and Date
      2011-09-17
    • Related Report
      2013 Final Research Report
  • [Presentation] IMPC参加に向けた各表現型解析センター間における行動表現型のデータ変換と比較2011

    • Author(s)
      古瀬民生, 他6名
    • Organizer
      第34回日本神経科学大会
    • Place of Presentation
      パシフィコ横浜(横浜市)
    • Year and Date
      2011-09-17
    • Related Report
      2011 Annual Research Report
  • [Presentation] なぜマウスクリニックは展開されるか2011

    • Author(s)
      若菜茂晴
    • Organizer
      第58回日本実験動物学会総会
    • Place of Presentation
      タワーホール船堀(東京都)
    • Year and Date
      2011-05-26
    • Related Report
      2013 Final Research Report 2011 Annual Research Report
  • [Presentation] 個体発生期の環境要因の差異による網羅的マウス表現型解析その1‐出産方法および里親による検討‐2011

    • Author(s)
      金田秀貴, 他11名
    • Organizer
      第58回日本実験動物学会総会
    • Place of Presentation
      タワーホール船堀(東京都)
    • Year and Date
      2011-05-25
    • Related Report
      2013 Final Research Report
  • [Presentation] 個体発生期の環境要因の差異による網羅的マウス表現型解析その1-出産方法および里親による検討-2011

    • Author(s)
      金田秀貴, 他11名
    • Organizer
      第58回日本実験動物学会総会
    • Place of Presentation
      タワーホール船堀(東京都)
    • Year and Date
      2011-05-25
    • Related Report
      2011 Annual Research Report
  • [Presentation] マウスモデルを用いたDOHaD仮説の実証2 : 母体低栄養が新生仔の行動表現型に与える影響

    • Author(s)
      古瀬民生, 幸田尚, 串田知子, 柏村実生, 山田郁子, 金田秀貴, 小林喜美男, 石野史敏, 古市貞一, 久保田健夫, 若菜茂晴
    • Organizer
      第60回日本実験動物学会総会
    • Place of Presentation
      つくば国際会議場(茨城県つくば市)
    • Related Report
      2013 Annual Research Report
  • [Presentation] マウス胎生期低栄養モデルからの知見

    • Author(s)
      古瀬民生, 若菜茂晴
    • Organizer
      第2回日本DOHaD研究会年会
    • Place of Presentation
      厚生労働省戸山研究庁舎(東京都新宿区)
    • Related Report
      2013 Annual Research Report
  • [Presentation] マウス胎児期低栄養曝露された新生仔の遺伝子発現と表現型解析

    • Author(s)
      若菜茂晴, 古瀬民生
    • Organizer
      第40回日本毒性学会学術年会
    • Place of Presentation
      幕張メッセ国際会議場(千葉県千葉市)
    • Related Report
      2013 Annual Research Report
    • Invited
  • [Presentation] マウスモデルを用いたDOHaD仮説の評価:母体低栄養が産仔の行動表現に与える影響

    • Author(s)
      古瀬民生
    • Organizer
      包括脳科学研究推進支援ネットワーク夏のワークショップ
    • Place of Presentation
      名古屋国際会議場(愛知県名古屋市)
    • Related Report
      2013 Annual Research Report
  • [Book] 疾患モデルマウス表現型解析指南2011

    • Author(s)
      山村研一、若菜茂晴 編
    • Total Pages
      477
    • Publisher
      中山書店
    • Related Report
      2013 Final Research Report
  • [Book] 疾患モデルマウス表現型解析指南2011

    • Author(s)
      山村研一、若菜茂晴編集
    • Total Pages
      477
    • Publisher
      中山書店
    • Related Report
      2011 Annual Research Report

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Published: 2011-06-18   Modified: 2019-07-29  

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