Whether hyperactivity disorder is genetic diseases or not? The establishment of gene diagnosis for hyperactivity disorder due to CIN85 abnormality.

• Project/Area Number: 24651219
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Medical genome science
• Research Institution: Gunma University
• Principal Investigator: SHIMOKAWA Noriaki 群馬大学, 医学(系)研究科(研究院), 准教授 (90235680)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000); Fiscal Year 2013: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2012: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
• Keywords: CIN85 / 多動症 / 精神遅滞 / X染色体連鎖性精神遅滞 / ヒトゲノム / 国際情報交換

Outline of Final Research Achievements

We found that human CIN85 gene exists to the short-arm of X chromosome. We also found that CIN85 co-localizes in neuronal dendritic spines with Oligophrenin 1 that is a responsible gene for X-linked mental retardation and with PSD-95 that is one of scaffold protein. Moreover, we had read the DNA sequence of CIN85 gene (approximately 360.7 kbp) from the genome of patients of hyperactivity disorder and X-linked mental retardation family that has been provide from Gottingen University and compared the sequence with that of normal person. As a result, we found a deficit of 31 bases to 13th exons of several male patients. This defect was deleted proline residues of the Proline-rich region required for binding with other proteins. In patients with X-linked mental retardation, loss of function of the Proline-rich region seems to be induced the disturbance to intracellular signal transduction of normal brain function.

Research Products

• [Journal Article] Altered cerebellum development and dopamine distribution in a rat genetic model with congenital hypothyroidism. (2014)
  • Author(s): Shimokawa N, Yousefi B, Morioka S, Yamaguchi S, Ohsawa A, Hayashi H, Azuma A, Mizuno H, Kasagi M, Masuda H, Jingu H, Furudate SI, Haijima A, Takatsuru Y, Iwasaki T, Umezu M, Koibuchi N.
  • Journal Title: J Neuroendocrinol. Volume: 26 Issue: 3 Pages: 164-175
  • DOI: 10.1111/jne.12135
  • Peer Reviewed / Open Access
• [Journal Article] Possible involvement of IGF-1 signaling on compensatory growth of the infraspinatus muscle induced by the supraspinatus tendon detachment of rat shoulder (2014)
  • Author(s): Ichinose T, Lesmana R, Yamamoto A, Kobayashi T, Shitara H, Shimoyama D, Takatsuru Y, Iwasaki T, Shimokawa N, Takagishi K, Koibuchi N
  • Journal Title: Physiological Rep Volume: 2 Issue: 1 Pages: 1-10
  • DOI: 10.1002/phy2.197
  • Peer Reviewed / Open Access
• [Journal Article] Early-life-stress affects the homeostasis of glutamatergic synapses. (2014)
  • Author(s): Toya S, Takatsuru Y, Kokubo M, Amano I, Shimokawa N, Koibuchi N.
  • Journal Title: Eur J Neurosci. Volume: 40 Issue: 11 Pages: 3627-34
  • DOI: 10.1111/ejn.12728
  • Peer Reviewed / Open Access
• [Journal Article] The effect of low dose lipopolysaccharide on thyroid hormone-regulated actin cytoskeleton modulation and type 2 iodothyronine deiodinase activity in astrocytes. (2013)
  • Author(s): Xu M, Iwasaki T, Shimokawa N, Sajdel-Sulkowska EM, Koibuchi N.
  • Journal Title: Endocrine Journal Volume: 60 Pages: 1221-1230
  • NAID: 130004770400
  • Peer Reviewed
• [Journal Article] Interaction of silencing mediator for retinoid and thyroid receptors with steroid and xenobiotic receptor on multidrug resistance 1 promoter (2013)
  • Author(s): Kazumi Hirooka-Masui
  • Journal Title: Life Sciences Volume: 92 Issue: 17-19 Pages: 911-915
  • DOI: 10.1016/j.lfs.2013.03.007
  • Peer Reviewed
• [Journal Article] Effects of perinatal lipopolysaccharide (LPS) exposure on the developing rat brain; modeling the effect of maternal infection on the developing human CNS. (2013)
  • Author(s): Xu M, Sulkowski ZL, Parekh P, Khan A, Chen T, Midha S, Iwasaki T, Shimokawa N, Koibuchi N, Zavacki AM, Sajdel-Sulkowska EM.
  • Journal Title: Cerebellum Volume: 12 Issue: 4 Pages: 572-586
  • DOI: 10.1007/s12311-013-0465-z
  • Peer Reviewed
• [Journal Article] Critical role of the astrocyte for functional remodeling in contralateral hemisphere of somatosensory cortex after stroke. (2013)
  • Author(s): Takatsuru Y, Eto K, Kaneko R, Masuda H, Shimokawa N, Koibuchi N, Nabekura J.
  • Journal Title: J Neurosci. Volume: 33 Issue: 11 Pages: 4683-4692
  • DOI: 10.1523/jneurosci.2657-12.2013
  • Peer Reviewed
• [Journal Article] Effects of Perinatal Lipopolysaccharide (LPS) Exposure on the Developing Rat Brain; Modeling the Effect of Maternal Infection on the Developing Human CNS. (2013)
  • Author(s): Xu M, Sulkowski ZL, Parekh P, Khan A, Chen T, Midha S, Iwasaki T, Shimokawa N, Koibuchi N, Zavacki AM, Sajdel-Sulkowska EM.
  • Journal Title: Cerebellum Volume: 12 Pages: 205-213
  • Peer Reviewed
• [Journal Article] CIN85 is a critical mediator in the regulation of behavior and metabolism. (2013)
  • Author(s): Shimokawa N.
  • Journal Title: Biomedical reports Volume: 4 Pages: 59-65
  • Peer Reviewed
• [Journal Article] Alterations of biochemical marker levels and myonuclear numbers in rat skeletal muscle after ischemia-reperfusion. (2012)
  • Author(s): Itoh M
  • Journal Title: Mol Cell Biochem. Volume: 373 Issue: 1-2 Pages: 11-18
  • DOI: 10.1007/s11010-012-1470-0
  • Peer Reviewed
• [Presentation] Lack of CIN causes impairment of maternal behaviour. (2014)
  • Author(s): Shimokawa N, Sairenji T, Kaneko R, Koibuchi N.
  • Organizer: 16th Congress of the European Neuroendocrine Association
  • Place of Presentation: Sofia, Bulgaria
  • Year and Date: 2014-09-10 – 2014-09-13
• [Presentation] Impairment of maternal behaviour by lack of CIN85. (2013)
  • Author(s): Shimokawa N, Ikezawa J, Masuda S, Koibuchi N.
  • Organizer: FENS Featured Regional Meeting
  • Place of Presentation: Prague, Czech Republic
• [Presentation] Decision mechanisms to child-rearing in fetal period. (2013)
  • Author(s): Shimokawa N.
  • Organizer: International Symposium on Prediction and Dicision Making 2013
  • Place of Presentation: Kyoto, Japan
• [Presentation] The cerebral glucose transporter SLC45A1 is mutated in individuals with non-syndromic intellectual disability and epilepsy. (2013)
  • Author(s): Srour M, Shimokawa N, Hamdan FF, Dobrzeniecka S, Rouleau GA, Poulin C, Michaud JL.
  • Organizer: American Society of Human Genitics 2013
  • Place of Presentation: Boston, MA, USA
• [Presentation] Impairment of rearing behaviors in CIN85-deficient mice (2013)
  • Author(s): 下川 哲昭、池澤 淳、増田 真之佑、鯉淵 典之
  • Organizer: 第90回日本生理学会大会
  • Place of Presentation: 東京
• [Presentation] 先天性甲状腺機能低下症（rdw）ラットの小脳機能に対するチロキシン経口投与の効果 (2013)
  • Author(s): 林 秀華、東 杏莉、水野 寛之、増田 真之佑、于 璐、レスマナ ロニー、蓜島 旭、高鶴 裕介、岩崎 俊晴、下川 哲昭、梅津 元昭、鯉淵 典之
  • Organizer: 第90回日本生理学会大会
  • Place of Presentation: 東京
• [Presentation] Lack of CIN85 in brain causes impared maternal behaviors by aberrant dopamine-prolactin signaling. (2012)
  • Author(s): Shimokawa N, Ikezawa J, Haglund K, Koibuchi N, Dikic I.
  • Organizer: The 4th EMBO meeting
  • Place of Presentation: Nice, France
• [Presentation] Aerobic training influences plasma concentration of thyroid hormone and potentiates thyroid hormone responsiveness to several genes in rat skeletal muscle. (2012)
  • Author(s): Lesmana R., Iwasaki T., Shimokawa N., Koibuchi N.
  • Organizer: 10th Asia and Oceania Thyroid Association Congress
  • Place of Presentation: Bali, Indonesia
• [Presentation] CIN85の機能欠損による行動異常の解析
  • Author(s): 下川 哲昭、池澤 淳、鯉淵 典之
  • Organizer: 平成24年度日本生化学会関東支部例会
  • Place of Presentation: 前橋、群馬
• [Presentation] CIN85欠損における胎仔期脳内環境の破綻と育仔放棄
  • Author(s): 下川 哲昭、池澤 淳、増田 真之佑、鯉淵 典之
  • Organizer: 第８回環境生理学プレコングレス
  • Place of Presentation: 東京
• [Remarks] 群馬大学医学系研究科 応用生理学分野
  • URL: http://nori3.dept.med.gunma-u.ac.jp/