Analysis of behavior disorder and the deficient rescue of CIN85 knockout mouse that shows hyperactivity and rearing neglect to newborns

2011 Fiscal Year Final Research Report

• Project/Area Number: 21590251
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Environmental physiology (including Physical medicine and Nutritional physiology)
• Research Institution: Gunma University
• Principal Investigator: SIMOKAWA Noriaki 群馬大学, 大学院・医学系研究科, 准教授 (90235680)
• Co-Investigator(Kenkyū-buntansha): KOIBUCHI Noriyuki 群馬大学, 大学院・医学系研究科, 教授 (80234681)
• Project Period (FY): 2009 – 2011
• Keywords: CIN85 / 多動性 / ドーパミン受容体 / エンドサイトーシス / ノックアウトマウス

Research Abstract

Cbl-interacting protein of 85 kDa (CIN85) is an adaptor protein implicated in the regulation of receptor trafficking and cell division. CIN85 knockout (CIN85 KO) mice displayed a hyperactivity phenotype. In CIN85 KO, the recruitment of the endocytic machinery required for D2DR endocytosis is diminished. Our findings indicate an important role of CIN85 in the regulation of dopamine receptor functions and provide new insight into a molecular explanation for hyperactive behavior.

Research Products

• [Journal Article] Ligand-induced down regulation of TrkA is partly regulated through ubiquitination by Cbl (2011)
  • Author(s): Takahashi Y, Shimokawa N, Esmaeili-Mahani S, Morita A, Masuda H, Iwasaki T, Tamura J, Haglund K, Koibuchi N
  • Journal Title: FEBS Lett Volume: 585 Pages: 1741-1747
  • Peer Reviewed
• [Journal Article] Suppression of thyroid hormone receptor-mediated transcription and disruption of thyroid hormone-induced cerebellar morphogenesis by the polybrominated biphenyl mixture (2011)
  • Author(s): Ibhazehiebo K, Iwasaki T, Okano-Uchida T, Shimokawa N, Ishizaki Y, Koibuchi N
  • Journal Title: Neurotoxicology Volume: 32 Pages: 400-409
  • Peer Reviewed
• [Journal Article] Brain-derived neurotrophic factor (BDNF) ameliorates the suppression of thyroid hormone-induced granule cell neurite extension by hexabromocyclododecane (HBCD) (2011)
  • Author(s): Ibhazehiebo K, Iwasaki T, Xu M, Shimokawa N, Koibuchi N
  • Journal Title: Neurosci Lett Volume: 493 Pages: 1-7
  • Peer Reviewed
• [Journal Article] 1,2,5,6,9,10-αHexabromocyclododecane (HBCD) impairs thyroid hormone-induced dendrite arborization of Purkinje cells and suppresses thyroid hormone receptor-mediated transcription (2011)
  • Author(s): Ibhazehiebo K, Iwasaki T, Shimokawa N, Koibuchi N
  • Journal Title: Cerebellum Volume: 10 Pages: 22-31
  • Peer Reviewed
• [Journal Article] Disruption of thyroid hormone receptor-mediated transcription and thyroid hormone-induced Purkinje cell dendrite arborization by polybrominated diphenylethers (2011)
  • Author(s): Ibhazehiebo K, Iwasaki T, Kimura-Kurods J, Miyazaki W, Shimokawa N, Koibuchi N
  • Journal Title: Environ Health Perspect Volume: 119 Pages: 168-75
  • Peer Reviewed
• [Journal Article] CIN85 regulates dopamine receptor endocytosis and governs behavior in mice (2010)
  • Author(s): Shimokawa N, Haglund K, Holter SM, Grabbe C, Kirkin V, Koibuchi N, Schultz C, Rozman J, Hoeller D, Qiu CH, Londono MB, Ikezawa J, Jedlicka P, Stein B, Schwarzacher WS, Wolfer PD, Ehrhardt N, Heuchel R, Nezis I, Brech A, Schmidt MH, Fuchs H, Gailus-Durner V, Klingenspor M, Bogler O, Wurst W, Deller T, Harbe de Angelis M, Dikic I
  • Journal Title: EMBO J Volume: 29 Pages: 2421-2432
  • Peer Reviewed
• [Journal Article] Hydroxylated PCB induces Ca^<2+> oscillations and alterations of membrane potential in cultured cortical cells (2010)
  • Author(s): Londono MB, Shimokawa N, Miyazaki W, Iwasaki T, Koibuchi N
  • Journal Title: J. Appl. Toxicol Volume: 30 Pages: 334-342
  • Peer Reviewed
• [Journal Article] The effect of hydroxylated PCB metabolites on TR-mediated transcription through native-TRE. Ind (2010)
  • Author(s): Amano I, Miyazaki W, Iwasaki T, Shimokawa N, Koibuchi N
  • Journal Title: Health Volume: 48 Pages: 115-118
  • Peer Reviewed
• [Journal Article] Activation of aromatase expression by retinoic acid receptor-related orphan receptor (ROR) τ in breast cancer cells: identification of a novel for response element (2009)
  • Author(s): Odawara H, Iwasaki T, Horiguchi J, Rokutanda N, Hirooka K, Miyazaki W, Koibuchi Y, Shimokawa N, Iino Y, Takeyoshi I, Koibuchi N
  • Journal Title: J. Biol. Chem Volume: 284 Pages: 17711-17719
  • Peer Reviewed
• [Journal Article] Retinoic Acid receptor-related orphan receptor alpha-enhanced thyroid hormone receptor-mediated transcription requires its ligand binding domain which is not, by itself, sufficient: possible direct interaction of two receptors (2009)
  • Author(s): Qiu CH, Miyazaki W, Iwasaki T, Londono M, Ibhazehiebo K, Shimokawa N, Koibuchi N
  • Journal Title: Thyroid Volume: 19 Pages: 893-898
  • Peer Reviewed
• [Presentation] Lack of CIN85 in brain leads to impaired dopamine receptor endocytosis and hyperactivity in mice (2012)
  • Author(s): 下川哲昭, 池澤淳, 増田寛子, 鯉淵典之
  • Organizer: 第89回日本生理学会大会
  • Place of Presentation: 松本
  • Year and Date: 2012-03-31
• [Presentation] Recent progress of the effect of Bromo-related environmental chemicals on thyroid hormone-related normal brain development (2012)
  • Author(s): 岩崎俊晴, イブハゼヒエボ キングスレイ, 原口瑞樹, 徐明, 下川哲昭, 鯉淵典之
  • Organizer: 第89回日本生理学会大会
  • Place of Presentation: 松本
  • Year and Date: 2012-03-31
• [Presentation] Effect of chronic aerobic exercise on thyroid hormone target genes in rat skeletal muscle (2012)
  • Author(s): レスマナロニー, 岩崎俊晴, 下川哲昭, 鯉淵典之
  • Organizer: 第89回日本生理学会大会
  • Place of Presentation: 松本
  • Year and Date: 2012-03-30
• [Presentation] Lack of CIN85 in brain leads to impaired dopamine receptor endocytosis and hyperactivity in mice (2011)
  • Author(s): Shimokawa N., Haglund K., Koibuchi N, Dikic I
  • Organizer: EMBO meeting
  • Place of Presentation: Vienna, Aurtria
  • Year and Date: 20110910-13
• [Presentation] 母乳を介した水酸化PCBの曝露は新生仔ラットで多動を引き起こす (2011)
  • Author(s): 下川哲昭昭, レスマナロニー, 高鶴裕介, 岩崎俊晴, 鯉淵典之
  • Organizer: 第14回環境ホルモン学会研究発表会
  • Place of Presentation: 東京
  • Year and Date: 2011-12-01
• [Presentation] CIN85の機能欠損はドーパミン受容体のエンドサイトーシスを抑制し多動を引き起こす (2011)
  • Author(s): 下川哲昭, 鯉淵典之
  • Organizer: 第58回北関東医学会総会
  • Place of Presentation: 前橋
  • Year and Date: 2011-09-29
• [Presentation] Disruption of cerebellar development by brominated organic chemicals possibly through suppression of TR-mediated transcription (2011)
  • Author(s): Iwasaki T., Ibhazehiebo K., Haraguchi M. Kimura-Kuroda J., Miyazaki W., Shimokawa N, Koibuchi N
  • Organizer: 4^<th> International Symposium Society for Research on the Cerebellum
  • Place of Presentation: Tokyo, Japan
  • Year and Date: 2011-09-18
• [Presentation] Cerebellar dysfunction and behavioral disorder in congenital hypothyroid (rdw) rat (2011)
  • Author(s): Yamaguchi S., Ohsawa A., Yousefi B., Morioka S., Masuda H., Ronny, Hayashi H., Takatsuru Y., Iwasaki T., Shimokawa N., Umezu M., Koibuchi N
  • Organizer: 4^<th> International Symposium Society for Research on the Cerebellum
  • Place of Presentation: Tokyo, Japan
  • Year and Date: 2011-09-18
• [Presentation] Lack of CIN85 in brain leads to impaired DRD2 endocytosis and hyperactivity (2010)
  • Author(s): Shimokawa N., Haglund K., Grabbe C, Koibuchi N, Dikic I
  • Organizer: EMBO Conference on Cellular Signaling & Molecular Medicine
  • Place of Presentation: Cavtat/Dubrovnik, Croatia
  • Year and Date: 20100521-26
• [Presentation] Defect of CIN85 suppresses mother's parenting behavior through dopamine-prolactin system (2010)
  • Author(s): Ikezawa J., Shimokawa N., Haglund K., Dikic I., Koibuchi N
  • Organizer: 14^<th. International Congress of Endocrinology
  • Place of Presentation: Kyoto, Japan
  • Year and Date: 20100326-30
• [Presentation] 受容体エンドサイトーシスにおけるCIN85の生理機能 (2010)
  • Author(s): 下川哲昭, 池澤淳, 増田寛子, 鯉淵典之
  • Organizer: 第87回日本生理学会大会
  • Place of Presentation: 盛岡
  • Year and Date: 2010-05-21
• [Presentation] Suppression of cerebellar Purkinje cell dendrite arborization by alpha-hexabromocyclododecane (2010)
  • Author(s): イブハゼヒエボキングスレイ, 岩崎俊晴, 下川哲昭, 木村-黒田純子, 鯉淵典之
  • Organizer: 第87回日本生理学会大会
  • Place of Presentation: 盛岡
  • Year and Date: 2010-05-20
• [Presentation] Excise intensity influences plasma concentration of thyroid hormone and expression of thyroid hormone receptor in muscles in rats (2010)
  • Author(s): ロニー, 下川哲昭, フェレニアレニー, 岩崎俊晴, 鯉淵典之
  • Organizer: 第87回日本生理学会大会
  • Place of Presentation: 盛岡
  • Year and Date: 2010-05-20
• [Presentation] The effect of lipopolysaccharide on astrocyte plasticity (2010)
  • Author(s): 徐明, 岩崎俊晴, 下川哲昭, 鯉淵典之
  • Organizer: 第87回日本生理学会大会
  • Place of Presentation: 盛岡
  • Year and Date: 2010-05-20
• [Presentation] Polybrominated diphenylethers (PBDEs) suppresses thyroid hormonereceptor (TR)-mediated transcription and impairs thyroid hormone (TH)-dependent dendrite arborization of Purkinje cells (2009)
  • Author(s): Ibhazehiebo K., Iwasaki T., Shimokawa N., Kimura-Kuroda J., Koibuchi N
  • Organizer: 9^<th> Asia and Oceania Thyroid Association Congress
  • Place of Presentation: Nagoya, Japan
  • Year and Date: 20091101-04
• [Presentation] Dynamics of the interaction of GR or TR with the general coactivator SYT (2009)
  • Author(s): Londono B. M., Iwasaki T., Ibhazehiebo K., Lizcano F., Shimokawa N., Koibuchi N
  • Organizer: 39^<th. Annual Meeting, Society for Neuroscience
  • Place of Presentation: Chicago, IL, USA
  • Year and Date: 20091017-21
• [Presentation] Suppression of thyroid hormone-induced dendrite arborization of Purkinje cells by polybrominated diphenyl ethers (2009)
  • Author(s): Koibuchi N., Ibhazehiebo K., Shimokawa N., Iwasaki T
  • Organizer: 39^<th> Annual Meeting, Society for Neuroscience
  • Place of Presentation: Chicago, IL, USA
  • Year and Date: 20091017-21
• [Presentation] CIN85 knockout mice are hyperactive due to defective dopamine receptor endocytosis in the brain (2009)
  • Author(s): Shimokawa N., Haglund K., Dikic I., Koibuchi N
  • Organizer: 36^<th> International Congress of Physiological Science
  • Place of Presentation: Kyoto, Japan
  • Year and Date: 20090727-0801
• [Presentation] Student laboratory practice through MD-PhD course (2009)
  • Author(s): Koibuchi N., Iwasaki T., Shimokawa N
  • Organizer: 36^<th> International Congress of Physiological Science
  • Place of Presentation: Kyoto, Japan
  • Year and Date: 20090727-0801
• [Presentation] Analysis of nursing ability and lactational functrion of CIN85 deficient mice (2009)
  • Author(s): Ikezawa J., Aotsuka N., Sayama K., Shimokawa N., Koibuchi N
  • Organizer: 36^<th> International Congress of Physiological Science
  • Place of Presentation: Kyoto, Japan
  • Year and Date: 20090727-0801
• [Presentation] Behavioral differences between congenital hypothyroid (rdw) and euthyroid rats (2009)
  • Author(s): Morioka S., Yamaguchi S., Kasagi M., Shimokawa N., Koibuchi N
  • Organizer: 36^<th> International Congress of Physiological Science
  • Place of Presentation: Kyoto, Japan
  • Year and Date: 20090727-0801
• [Presentation] Low dose polybrominated diphenylethers (PBDEs) suppresses thyroid hormone receptor (TR)-mediated transcription via DNA binding domain (2009)
  • Author(s): Ibhazehiebo K., Iwasaki T., Londono B.M., Hirooka K., Kimura-Kuroda J., Shimokawa N., Koibuchi N
  • Organizer: 36^<th> International Congress of Physiological Science
  • Place of Presentation: Kyoto, Japan
  • Year and Date: 20090727-0801
• [Presentation] Ischemia-reperfusion changes in skeletal muscle morphology (2009)
  • Author(s): Itoh M., Shimokawa N., Tajika Y., Murakami T., Yorifuji H., Koibuchi N
  • Organizer: 36^<th> International Congress of Physiological Science
  • Place of Presentation: Kyoto, Japan
  • Year and Date: 20090727-0801
• [Presentation] Intracellular trafficking go the general coactivator SYT (2009)
  • Author(s): Londono B.M., Iwasaki T., Ibhazehiebo K., Shimokawa N., Koibuchi N
  • Organizer: 36^<th> International Congress of Physiological Science
  • Place of Presentation: Kyoto, Japan
  • Year and Date: 20090727-0801
• [Presentation] The mechanism of the gender difference of PCB action of thyroid hormone receptor interaction (2009)
  • Author(s): Ogawa A., Iwasaki T., Kikuchi T., Ibhazehiebo K., Hirooka K., Shimokawa N., Sajdel-Sulkowska E.M., Koibuchi N
  • Organizer: 36^<th> International Congress of Physiological Science
  • Place of Presentation: Kyoto, Japan
  • Year and Date: 20090727-0801
• [Presentation] CIN85機能欠失による受容体エンドサイトーシスの解析シンポジウム「エンドサイトーシスによる細胞機能の制御」 (2009)
  • Author(s): 下川哲昭
  • Organizer: 第82回日本生化学会大会
  • Place of Presentation: 神戸
  • Year and Date: 2009-10-21
• [Presentation] Synovial sarcoma translocation (SYT)と核内ホルモン受容体のリガンド存在下における細胞内の動態 (2009)
  • Author(s): 岩崎俊晴, Marina B. Londono, Kingsley Ibhazehiebo, 下川哲昭, 鯉淵典之
  • Organizer: 第56回北関東医学会総会
  • Place of Presentation: 前橋
  • Year and Date: 2009-10-08
• [Presentation] Low dose hexabromocyclododecane suppress thyroid hormone receptor-mediated transcription (2009)
  • Author(s): イブハゼヒエボキングスレイ, 岩崎俊晴, ロンドニョマリーナ, 広岡和美, 下川哲昭, 鯉淵典之
  • Organizer: 第82回日本内分泌学会学術総会
  • Place of Presentation: 前橋
  • Year and Date: 2009-04-25
• [Presentation] Imaging analysis of the general coactivator SYT in living cells (2009)
  • Author(s): ロンドニョマリーナ, 岩崎俊晴, イブハゼヒエボキングスレイ, 下川哲昭, 鯉淵典之
  • Organizer: 第82回日本内分泌学会学術総会
  • Place of Presentation: 前橋
  • Year and Date: 2009-04-25
• [Book] インテグレーテッドシリーズ生理学 (2011)
  • Author(s): 下川哲昭
  • Total Pages: 249
  • Publisher: 東京化学同人
• [Book] 内分泌・栄養・代謝系コア・カリキュラムテキスト」:性ホルモンの合成・代謝経路と作用 (2011)
  • Author(s): 下川哲昭
  • Total Pages: 343
  • Publisher: 文光堂
• [Book] 「症例問題から学ぶ生理学・原著3版」:細胞および自律生理学 (2009)
  • Author(s): 下川哲昭
  • Total Pages: 392
  • Publisher: 丸善株式会社
• [Remarks]
  • URL: http://nori3.dept.med.gunma-u.ac.jp/index.php?イベント