Establishing model mouse for anxiety disorders using a novel wild-derived heterogeneous stock

• Project/Area Number: 15H04289
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Laboratory animal science
• Research Institution: National Institute of Genetics
• Principal Investigator: Koide Tsuyoshi 国立遺伝学研究所, 系統生物研究センター, 准教授 (20221955)
• Co-Investigator(Renkei-kenkyūsha): TANAVE Akira 大学共同利用機関法人情報・システム研究機構, 新領域融合研究センター, 融合プロジェクト特任研究員 (30749023) ; TAKAHASHI Aki 筑波大学, 人間系, 助教 (30581764) ; HORII Yasuyuki 国立遺伝学研究所, 系統生物研究センター, 博士研究員 (50601960)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥16,640,000 (Direct Cost: ¥12,800,000、Indirect Cost: ¥3,840,000); Fiscal Year 2017: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000); Fiscal Year 2016: ¥5,720,000 (Direct Cost: ¥4,400,000、Indirect Cost: ¥1,320,000); Fiscal Year 2015: ¥6,370,000 (Direct Cost: ¥4,900,000、Indirect Cost: ¥1,470,000)
• Keywords: 野生マウス / 不安様行動 / 多因子疾患 / QTL解析 / ゲノム / 遺伝子マッピング / 能動的従順性 / 家畜化 / 選択交配 / マウス / 従順性 / 遺伝子 / マッピング / 量的形質 / ヘテロジニアスストック / 遺伝学 / 精神疾患 / モデル動物 / 遺伝子発現 / アウトブレッドストック / 行動 / 野生系統 / 多因子形質 / アウトブレッド

Outline of Final Research Achievements

A novel wild - derived heterogeneous stock (WHS) was established by genetically mixing with eight wild strains. We conducted selective breeding for active tameness to humans and selected and non - selected groups were successfully established. By conducting SNP analysis using genomic DNA on these selected and non-selected groups of mice, we performed genetic analysis for active tameness. We found genetic loci relating to active tameness on chromosome 11. In order to narrowing down the loci, we conducted comparative analysis of mouse and dog genome. We found that the data of the selected region showed high degree of overlap with the genomic regions which were selected during the evolution of dog breeds.

Research Products

• [Int'l Joint Research] University College London(United Kingdom)
• [Journal Article] Hierarchy in the home cage affects behaviour and gene expression in group-housed C57BL/6 male mice. (2017)
  • Author(s): Horii Y, Nagasawa T, Sakakibara H, Takahashi A, Tanave A, Matsumoto Y, Nagayama H, Yoshimi K, Yasuda MT, Shimoi K, Koide T.
  • Journal Title: Scientific Reports Volume: 7 Issue: 1 Pages: 6991-6991
  • DOI: 10.1038/s41598-017-07233-5
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Selective breeding and selection mapping using a novel wild-derived heterogeneous stock of mice revealed two closely-linked loci for tameness. (2017)
  • Author(s): Matsumoto, Y., Goto, T., Nishino, J., Nakaoka, H., Tanave, A., Takano-Shimizu, T., Mott, R. F., and Koide, T.
  • Journal Title: Scientific Reports Volume: 7 Issue: 1 Pages: 4607-4607
  • DOI: 10.1038/s41598-017-04869-1
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Pup exposure facilitates retrieving behavior via the oxytocin neural system in female mice (2017)
  • Author(s): Okabe, S., Tsuneoka, Y., Takahashi, A., Ooyama, R., Watarai, A., Maeda, S., Honda, Y., Nagasawa, M., Mogi, K., Nishimori, K., Kuroda, M., Koide, T., Kikusui, T.
  • Journal Title: Psychoneuroendocrinology Volume: 79 Pages: 20-30
  • DOI: 10.1016/j.psyneuen.2017.01.036
  • Peer Reviewed / Open Access
• [Journal Article] Automated Estimation of Mouse Social Behaviors Based on a Hidden Markov Model. (2017)
  • Author(s): Arakawa T, Tanave A, Takahashi A, Kakihara S, Koide T, Tsuchiya T.
  • Journal Title: Methods in Molecular Biology Volume: 1552 Pages: 185-197
  • DOI: 10.1007/978-1-4939-6753-7_14
  • ISBN: 9781493967513, 9781493967537
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Caspr3-Deficient Mice Exhibit Low Motor Learning during the Early Phase of the Accelerated Rotarod Task. (2016)
  • Author(s): Hirata H, Takahashi A, Shimoda Y, Koide T.
  • Journal Title: PLoS One Volume: 11 Issue: 1 Pages: e0147887-e0147887
  • DOI: 10.1371/journal.pone.0147887
  • NAID: 120007129617
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Cell adhesion molecule Caspr3 is expressed in the mouse basal ganglia during early postnatal stages. (2016)
  • Author(s): Hirata, H., Umemori, J., Yoshioka, H., Koide, T., Watanabe, K., Shimoda, Y.
  • Journal Title: Journal of Neuroscience Research Volume: 94 Issue: 1 Pages: 74-89
  • DOI: 10.1002/jnr.23670
  • Peer Reviewed
• [Journal Article] Mapping of genetic factors that elicit intermale aggressive behavior on Mouse Chromosome 15: intruder effects and the complex genetic basis (2015)
  • Author(s): Takahashi, A., Sugimoto, H., Kato, S., Shiroishi, T. and Koide, T.
  • Journal Title: PLOS ONE Volume: 10(9): e0137764 Issue: 9 Pages: 1-20
  • DOI: 10.1371/journal.pone.0137764
  • Peer Reviewed / Open Access
• [Journal Article] Glutamate input in the dorsal raphe nucleus as a determinant of escalated aggression in male mice. (2015)
  • Author(s): Takahashi, A., Lee, R.X., Iwasato, T., Itohara, S., Arima, H., Bettler, B., Miczek, K.A., Koide, T.
  • Journal Title: The Journal of Neuroscience Volume: 35 Pages: 6452-6463
  • NAID: 120007130264
  • Peer Reviewed / Int'l Joint Research
• [Presentation] ヒトになつくマウスの行動・生理・神経および遺伝的基盤 (2017)
  • Author(s): 小出剛
  • Organizer: 第95回日本生理学会大会
  • Invited
• [Presentation] 選択交配マウスを用いて明らかにする動物家畜化の遺伝的基盤 (2017)
  • Author(s): 小出剛
  • Organizer: 日本畜産学会第124回大会
  • Invited
• [Presentation] マウスにおけるテイム行動の遺伝学的・行動学的および神経学的基盤の解明に向けて (2017)
  • Author(s): 小出剛
  • Organizer: 第27回日本行動神経内分泌研究会
• [Presentation] RNA-seqを用いたマウスの従順性に関わる遺伝的基盤の解明 (2017)
  • Author(s): 松本悠貴、中岡博史、永山博通、小出剛
  • Organizer: 第64回日本実験動物学会総会
• [Presentation] 長鎖一本鎖DNAを用いたリピート配列改変マウスの作製 (2017)
  • Author(s): 吉見一人、田邉彰、今井悠二、二瓶基子、小出剛
  • Organizer: 第64回日本実験動物学会総会
• [Presentation] Neurobehavioral study for relationship between sociability and tameness in domesticated mice (2017)
  • Author(s): Nagayama H, Matsumoto Y, Koide T
  • Organizer: 第40回日本神経科学大会
• [Presentation] Behavioral analysis of fear in PACAP over-expression mice (2017)
  • Author(s): Tanave A, Koide T
  • Organizer: 第40回日本神経科学大会
• [Presentation] PACAP遺伝子改変マウスにおける情動行動および恐怖記憶学習の解析 (2017)
  • Author(s): 田邉彰、小出剛
  • Organizer: 第47回日本神経精神薬理学会
• [Presentation] 野生由来マウス集団の選択交配による高度な従順化とその関連遺伝子座解析 (2017)
  • Author(s): 小出剛、永山博通、後藤達彦、松本悠貴
  • Organizer: 第77回日本動物心理学会
• [Presentation] マウスの能動的従順性（人に対する接触行動）に関わる行動特性および神経基盤の解析 (2017)
  • Author(s): 永山博通、松本悠貴、小出剛
  • Organizer: 第77回日本動物心理学会
• [Presentation] Hunting genetic factors associated with high anxiety-like behavior in wild mouse strain (2016)
  • Author(s): Koide T.
  • Organizer: 第46回日本神経精神薬理学会
  • Invited
• [Presentation] Genetic variation and expression diversity of pituitary adenylate cyclase-activating polypeptide (PACAP) gene in mouse (2016)
  • Author(s): Koide T., Tanave A.
  • Organizer: 30th CINP World Congress of Neuropsychopharmacology
  • Int'l Joint Research
• [Presentation] High expression of PACAP gene and the molecular mechanism found in wild-mouse strain showing elevated anxiety-like behavior (2016)
  • Author(s): Tanave A., Koide T., Sumiyama, K., Takahashi, A.
  • Organizer: 30th CINP World Congress of Neuropsychopharmacology
  • Int'l Joint Research
• [Presentation] Expression diversity and genetic variation of pituitary adenylate cyclase-activating polypeptide (PACAP) gene in mouse (2016)
  • Author(s): Tanave, A., Koide T.
  • Organizer: The 39th Annual Meeting of the Japan Neuroscience Society
• [Presentation] Behavioral and neurological bases of tameness in selection groups of wild-derived heterogeneous stock (2016)
  • Author(s): Nagayama, H., Matsumoto, Y., Goto, T., Koide T.
  • Organizer: The 39th Annual Meeting of the Japan Neuroscience Society
• [Presentation] 長鎖一本鎖オリゴを用いたノックイン動物作製法の開発 (2016)
  • Author(s): 吉見一人、今井悠二、田邉彰、真下知士、小出剛
  • Organizer: The 88th Annual Meeting of the Genetics Society of Japan
• [Presentation] Selection mappingおよび関連解析によるマウス従順性関連遺伝領域の同定 (2016)
  • Author(s): 松本悠貴、西野譲、中岡博史、後藤達彦、小出剛
  • Organizer: The 88th Annual Meeting of the Genetics Society of Japan
• [Presentation] 野生由来マウスヘテロジニアスストックの選択交配によりみられる従順性の解析 (2016)
  • Author(s): 永山博通、松本悠貴、後藤達彦、小出剛
  • Organizer: The 63rd Annual Meeting of Japanese Association for Animal Science
• [Presentation] 野生ハツカネズミの下垂体アデニル酸シクラーゼ活性化ポリペプチド(PACA)遺伝子における正の自然選択 (2016)
  • Author(s): 田邉彰、小出剛
  • Organizer: The 63rd Annual Meeting of Japanese Association for Animal Science
• [Presentation] マウスの従順性行動に関わる遺伝子座とイヌの家畜化との関連 (2016)
  • Author(s): 松本悠貴、西野譲、後藤達彦、小出剛
  • Organizer: The 63rd Annual Meeting of Japanese Association for Animal Science
• [Presentation] マウス・ラットにおける長鎖一本鎖オリゴを用いた効率的なノックイン (2016)
  • Author(s): 吉見一人、今井悠二、田邉彰、真下知士、小出剛
  • Organizer: The 63rd Annual Meeting of Japanese Association for Animal Science
• [Presentation] Establishing new mouse resource, wild-derived heterogeneous stock, which is useful for genetic analysis of tameness and other complex traits. (2015)
  • Author(s): Koide, T., Matsumoto, Y., Nakaoka, H., Nishino, J., Goto, T.
  • Organizer: 29th International Mammalian Genome Conference
  • Place of Presentation: Yokohama
  • Year and Date: 2015-11-08
  • Int'l Joint Research
• [Presentation] CRISPR/Cas9-mediated plasmid knock-in and replacement of genomic region with single stranded oligonucleotides in rodents (2015)
  • Author(s): Yoshimi, K., Kaneko, T., Koide, T., Mashimo, T.
  • Organizer: 29th International Mammalian Genome Conference
  • Place of Presentation: Yokohama
  • Year and Date: 2015-11-08
  • Int'l Joint Research
• [Presentation] Combination of selective breeding and genome-wide SNP analysis revealed the genetic loci associated with tame behavior in mice (2015)
  • Author(s): Matsumoto, Y., Nakaoka, H., Nishino, J., Goto, T., Koide, T.
  • Organizer: 29th International Mammalian Genome Conference
  • Place of Presentation: Yokohama
  • Year and Date: 2015-11-08
  • Int'l Joint Research
• [Presentation] Higher expression of PACAP gene is associated with altered behavioral and prolonged physiological responses to stress in wild-derived MSM mice (2015)
  • Author(s): Tanave, A., Takahashi, A., Sumiyama, K., Koide, T.
  • Organizer: 29th International Mammalian Genome Conference
  • Place of Presentation: Yokohama
  • Year and Date: 2015-11-08
  • Int'l Joint Research
• [Presentation] 野生由来ヘテロジニアスストックを用いた遺伝学的解析の試み (2015)
  • Author(s): 小出剛、後藤達彦、松本悠貴
  • Organizer: 第87回日本遺伝学会大会
  • Place of Presentation: 仙台
  • Year and Date: 2015-09-24
• [Presentation] 選択交配およびゲノムワイド遺伝解析によるマウスの従順性行動に関わる遺伝子座の同定 (2015)
  • Author(s): 松本悠貴、中岡博史、西野穣、後藤達彦、小出剛
  • Organizer: 第87回日本遺伝学会大会
  • Place of Presentation: 仙台
  • Year and Date: 2015-09-24
• [Presentation] 野生由来ヘテロジニアスストックマウスの選択交配によりみられる従順性と不安、新奇探索性、社会生との関連 (2015)
  • Author(s): 永山博通、松本悠貴、後藤達彦、小出剛
  • Organizer: 第23回日本行動神経内分泌研究会
  • Place of Presentation: 仙台
  • Year and Date: 2015-09-18
• [Presentation] A series of behavioral analyses to reveal behavioral and psychological basis underlying tameness in selected population of wild-derived heterogeneous stock (WHS) of mice (2015)
  • Author(s): 永山博通、松本悠貴、後藤達彦、小出剛
  • Organizer: 日本動物心理学会 第75回大会
  • Place of Presentation: 東京
  • Year and Date: 2015-09-10
• [Presentation] Differences of sensitivity to anxiolytic effect of diazepam in wild-derived mouse strains (2015)
  • Author(s): Koide, T., Imai, Y., Hanzawa, N.
  • Organizer: 第38回日本神経科学大会
  • Place of Presentation: 神戸
  • Year and Date: 2015-07-28
• [Presentation] PACAP遺伝子発現によるストレス関連行動の調節の遺伝学的解析 (2015)
  • Author(s): 田邉彰、高橋阿貴、隅山健太、小出剛
  • Organizer: 第38回日本神経科学大会
  • Place of Presentation: 神戸
  • Year and Date: 2015-07-28
• [Presentation] 雄マウスの集団飼育下における社会的順位が海馬の神経新生に及ぼす影響 (2015)
  • Author(s): 堀井康行、長澤達弘、田邉彰、高橋阿貴、下位香代子、小出剛
  • Organizer: 第38回日本神経科学大会
  • Place of Presentation: 神戸
  • Year and Date: 2015-07-28
• [Presentation] Finding the Genetic Loci Associated with Tameness Using the Combination Method of Selective Breeding and Computer Simulation in Mice (2015)
  • Author(s): Matsumoto, Y., Nishino, J., Goto, T., Koide, T.
  • Organizer: Vth International Wildlife Management Congress 2015
  • Place of Presentation: 札幌
  • Year and Date: 2015-07-26
  • Int'l Joint Research
• [Presentation] 集団飼育下で社会的順位が最下位の雄マウスは,最上位の個体と比べて不安様・うつ様形質を示す (2015)
  • Author(s): 堀井康行、長澤達弘、田邉彰、高橋阿貴、下位香代子、小出剛
  • Organizer: 第62回日本実験動物学会総会
  • Place of Presentation: 京都
  • Year and Date: 2015-05-28
• [Presentation] MSM/Msマウスの不安様行動関連遺伝子の同定とその機能解析 (2015)
  • Author(s): 田邉彰、高橋阿貴、隅山健太、小出剛
  • Organizer: 第62回日本実験動物学会総会
  • Place of Presentation: 京都
  • Year and Date: 2015-05-28
• [Presentation] 選択交配およびコンピュータシミュレーションを用いた従順性行動に関わる遺伝子座の同定 (2015)
  • Author(s): 松本悠貴、西野穣、後藤達彦、小出剛
  • Organizer: 第62回日本実験動物学会総会
  • Place of Presentation: 京都
  • Year and Date: 2015-05-28
• [Book] マウス表現型解析スタンダード (2016)
  • Author(s): 伊川 正人、若菜 茂晴、高橋 智
  • Total Pages: 347
  • Publisher: 羊土社
  • ISBN: 9784758101981
• [Book] 個性は遺伝子で決まるのか (2015)
  • Author(s): 小出剛
  • Total Pages: 192
  • Publisher: ベレ出版
• [Remarks] 家畜動物はなぜ人になつくのか～人に近づくマウスをつくり遺伝のしくみを解明～
  • URL: https://www.nig.ac.jp/nig/ja/2017/07/research-highlights_ja/20170705.html