Establishment of conditional knockout animal model for analyzing the pathogenesis of follicular cyst in the goat.

• Project/Area Number: 23658223
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Applied animal science
• Research Institution: Nagoya University
• Principal Investigator: OHKURA Satoshi 名古屋大学, 生命農学研究科, 教授 (20263163)
• Co-Investigator(Renkei-kenkyūsha): FURUSAWA Tadashi 独立行政法人農業生物資源研究所, 動物科学研究領域, 研究員 (00343997)
• Research Collaborator: MATSUDA Fuko 名古屋大学, 大学院・生命農学研究科, 准教授 (10608855)
• Project Period (FY): 2011 – 2013
• Project Status: Completed (Fiscal Year 2013)
• Budget Amount: ¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000); Fiscal Year 2013: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000); Fiscal Year 2012: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000); Fiscal Year 2011: ¥2,730,000 (Direct Cost: ¥2,100,000、Indirect Cost: ¥630,000)
• Keywords: 応用動物 / 神経科学 / 獣医学 / 生理学 / 畜産学 / ヤギ / キスペプチン / 卵胞嚢腫

Research Abstract

In the present study, as the initial step in establishing a region-specific, conditional KISS1 gene knockout goat, we first revealed the genomic sequence of goat KISS1 gene 5'-upstream region up to 3 kb from translation initiation site. This information can be used for further evaluation of the promoter activity of goat KISS1 gene expression and establishment of conditional knockout model. Second, we demonstrated that an intravenous infusion of estrogen induced surge-like luteinizing hormone (LH) release both in gonadectomized male and female goats, and kisspeptin neurons in the medial preoptic area (mPOA) were activated by estrogen. In castrated male goats, mean peak LH concentration was lower and mean peak time of the LH surge was later than females. These results suggest that deterioration in functioning of mPOA kisspeptin neurons in response to estrogen in male goats can be applied as a model for analyzing the neuronal pathogenesis of follicular cyst in female ruminants.

Research Products

• [Journal Article] Molecular Cloning and Identification of the Transcriptional Regulatory Domain of the Goat Neurokinin B Gene <i>TAC3</i> (2013)
  • Author(s): Suetomi, Y., Matsuda, F., Uenoyama, Y., Maeda, K.-I., Tsukamura, H. and Ohkura, S.
  • Journal Title: Journal of Reproduction and Development Volume: 59 Issue: 5 Pages: 463-469
  • DOI: 10.1262/jrd.2013-037
  • NAID: 130003361048
  • ISSN: 0916-8818, 1348-4400
  • Peer Reviewed
• [Journal Article] Effects of Full-Length Kisspeptin Administration on Follicular Development in Japanese Black Beef Cows (2013)
  • Author(s): Naniwa, Y., Nakatsukasa, K., Setsuda, S., Oishi, S., Fujii, N., Matsuda, F., Uenoyama, Y., Tsukamura, H., Maeda, K. -I. and Ohkura, S.
  • Journal Title: Journal of Reproduction and Development Volume: 59 Issue: 6 Pages: 588-594
  • DOI: 10.1262/jrd.2013-064
  • NAID: 130003381852
  • ISSN: 0916-8818, 1348-4400
  • Peer Reviewed
• [Journal Article] Differential Effects of Continuous Exposure to the Investigational Metastin/Kisspeptin Analog TAK-683 on Pulsatile and Surge Mode Secretion of Luteinizing Hormone in Ovariectomized Goats (2013)
  • Author(s): Tanaka, T., Ohkura, S., Wakabayashi, Y., Kuroiwa, T., Nagai, K., Endo, N., Tanaka, A., Matsui, H., Kusaka, M. and Okamura, H.
  • Journal Title: Journal of Reproduction and Development Volume: 59 Issue: 6 Pages: 563-568
  • DOI: 10.1262/jrd.2013-060
  • NAID: 130003361063
  • ISSN: 0916-8818, 1348-4400
  • Peer Reviewed
• [Journal Article] Effect of peripherally administered kisspeptin-10 on GnRH neurosecretion into the hypophyseal portal circulation in ovariectomized goat does. (2012)
  • Author(s): Tanaka, T., Ohkura, S., Wakabayashi, Y. and Okamura, H.
  • Journal Title: Small Ruminant Research Volume: 105 Issue: 1-3 Pages: 273-276
  • DOI: 10.1016/j.smallrumres.2012.01.007
  • Peer Reviewed
• [Journal Article] 繁殖障害の根本治療に向けての新たな方法論 : KNDyニューロンの応用 (2012)
  • Author(s): 前多敬一郎・大蔵 聡・松田二子・難波陽介・若林嘉浩・岡村裕昭・井上直子・上野山賀久・束村博子
  • Journal Title: 家畜診療 Volume: 59 (7) Pages: 387-393
  • NAID: 40019379912
  • URL: http://www.nosai.or.jp/nosai/modules/pico/index.php?content_id=125&PHPSESSID=3d6e14b3ef9f35ef86e1661902e43e7b
• [Journal Article] Central Administration of Neurokinin B Activates Kisspeptin/NKB Neurons in the Arcuate Nucleus and Stimulates Luteinizing Hormone Secretion in Ewes During the Non-Breeding Season (2012)
  • Author(s): Sakamoto K, Murata K, Wakabayashi Y, Yayou K, Ohkura S, Takeuchi Y, Mori Y, Okamura H.
  • Journal Title: Journal of Reproduction and Development Volume: 58 Issue: 6 Pages: 700-706
  • DOI: 10.1262/jrd.2011-038
  • NAID: 10031146934
  • ISSN: 0916-8818, 1348-4400
  • Peer Reviewed
• [Journal Article] Follicular Growth and Atresia in Mammalian Ovaries: Regulation by Survival and Death of Granulosa Cells (2012)
  • Author(s): Matsuda, F., Inoue, N., Manabe, N. and Ohkura, S.
  • Journal Title: Journal of Reproduction and Development Volume: 58 Issue: 1 Pages: 44-50
  • DOI: 10.1262/jrd.2011-012
  • NAID: 10030407021
  • ISSN: 0916-8818, 1348-4400
  • Peer Reviewed
• [Journal Article] 繁殖障害の根本治療に向けての新たな方法論：KNDyニューロンの応用. (2012)
  • Author(s): 前多敬一郎・大蔵 聡・松田二子・難波陽介・若林嘉浩・岡村裕昭・井上直子・上野山賀久・束村博子
  • Journal Title: 家畜診療 Volume: 59 Pages: 387-393
  • NAID: 40019379912
• [Journal Article] Central distribution of kiss2 neurons and peri-pubertal changes in their expression in the brain of the male and female red seabream Pagrus major (2011)
  • Author(s): Shimizu, Y., Tomikawa, J., Hirano, K., Nanikawa, Y., Akazome, Y., Kanda, S., Kazeto, Y., Okuzawa, K., Uenoyama, Y., Ohkura, S., Tsukamura, H., Maeda, K.-I., Gen, K., Oka, Y., and Yamamoto, N.
  • Journal Title: General and Comparative Endocrinology Volume: 175 Issue: 3 Pages: 432-442
  • DOI: 10.1016/j.ygcen.2011.11.038
  • Peer Reviewed
• [Journal Article] Morphological evidence for direct interaction between kisspeptin and gonadotropin-releasing hormone neurons at the median eminence of the male goat: an immunoelectron microscopic study. (2011)
  • Author(s): Matsuyama S, Ohkura S, Mogi K, Wakabayashi Y, Mori Y, Tsukamura H, Maeda K, Ichikawa M, Okamura H.
  • Journal Title: Neuroendocrinology Volume: 94 Issue: 4 Pages: 323-332
  • DOI: 10.1159/000331576
  • Peer Reviewed
• [Journal Article] 卵胞発育の中枢制御機構 (2011)
  • Author(s): 井上直子・上野山賀久・大蔵 聡・束村博子・前多敬一郎
  • Journal Title: Hormone Frontier in Gynecology Volume: 18 Pages: 39-42
• [Presentation] 高濃度エストロジェン投与が去勢雄ウシのLH分泌におよぼす影響 (2014)
  • Author(s): 佐々木拓弥・松山秀一・木村康二・上野山賀久・束村博子・松田二子・大蔵 聡
  • Organizer: 日本畜産学会第118回大会
  • Place of Presentation: 茨城県つくば市
• [Presentation] Estrogen induces surge-like luteinizing hormone secretion in gonadectomized male and female goats : involvement of kisspeptin neurons in the medial preoptic area in both sexes (2013)
  • Author(s): Ohkura, S
  • Organizer: The 46th Annual Meeting of the Society for the Study of Reproduction
  • Place of Presentation: Montreal, Canada
  • Year and Date: 2013-07-24
• [Presentation] 去勢雄シバヤギ視索前野のキスペプチンニューロンは高濃度エストロジェンにより誘起されるサージLH 分泌を仲介する (2013)
  • Author(s): 末富祐太
  • Organizer: 日本畜産学会第116回大会
  • Place of Presentation: 広島県広島市
  • Year and Date: 2013-03-28
• [Presentation] Estrogen induces surge-like luteinizing hormone secretion in gonadectomized male and female goats: involvement of kisspeptin neurons in the medial preoptic area in both sexes. (2013)
  • Author(s): Ohkura, S., Nakatsukasa, K., Suetomi Y., Naniwa, Y., Ito, D., Inoue, N., Wakabayashi, Y., Okamura, H., Maeda, K.-I., Uenoyama, Y., Tsukamura, H. and Matsuda, F.
  • Organizer: The 46th Annual Meeting of the Society for the Study of Reproduction
  • Place of Presentation: Montreal, Canada
• [Presentation] Kisspeptin neurons in the medial preoptic area of castrated male goats mediate the surge-like luteinizing hormone secretion induced by acute elevations in circulating estrogen (2012)
  • Author(s): Nakatsukasa, K
  • Organizer: The 2nd World Conference on Kisspeptin Signaling in the Brain
  • Place of Presentation: Tokyo, Japan
  • Year and Date: 2012-11-07
• [Presentation] 動物の生殖機能を制御する神経内分泌メカニズム (2012)
  • Author(s): 大蔵 聡
  • Organizer: 第153回日本獣医学会学術集会
  • Place of Presentation: 埼玉県さいたま市
  • Year and Date: 2012-03-27
• [Presentation] キスペプチン／KNDyニューロンを応用した新たな繁殖制御技術の可能性. (2012)
  • Author(s): 大蔵 聡
  • Organizer: 第23回牛学術セミナー
  • Place of Presentation: 岡山市、さいたま市、札幌市、鹿児島市、郡山市、名古屋市
  • Invited
• [Presentation] 動物の生殖機能を制御する神経内分泌メカニズム (2012)
  • Author(s): 大蔵 聡
  • Organizer: 第153回日本獣医学会学術集会(招待講演)
  • Place of Presentation: さいたま、大宮ソニックシティ
• [Presentation] Male kisspeptin neuronal network and its interaction with GnRH neurons in goats (2011)
  • Author(s): Ohkura, S
  • Organizer: The 2nd World Congress on Reproductive Biology
  • Place of Presentation: Cairns, Australia
  • Year and Date: 2011-10-11
• [Presentation] Effects of metastin/kisspeptin analog, TAK-683, on luteinizing hormone secretion in peripheral plasma, and gonadotropin-releasing hormone secretion in the pituitary portal circulation in goats. (2011)
  • Author(s): Ohkura, S., Tanaka, T., Kuroiwa, T. Wakabayashi, Y., Ohtaki, T., Kusaka, M. and Okamura, H.
  • Organizer: The Endocrine Society 93rd Annual Meeting & Expo (ENDO 2011)
  • Place of Presentation: Boston, USA、Boston Convention & Exhibition Center
• [Presentation] Effects of chronic administration of a metastin analog, TAK-683, on the GnRH pulse generator activity in ovariectomized goats. (2011)
  • Author(s): Wakabayashi, Y., Yamamura, T., Ohkura, S., Tanaka, T., Kusaka, M. and Okamura, H.
  • Organizer: The Endocrine Society 93rd Annual Meeting & Expo (ENDO 2011)
  • Place of Presentation: Boston, USA、Boston Convention & Exhibition Center
• [Presentation] Neuroendocrine control of reproduction in goats. (2011)
  • Author(s): Ohkura, S.
  • Organizer: The Symposium on Animal Behavior and Control Mechanism, 2011(招待講演)
  • Place of Presentation: Linyi, China、Linyi University
• [Presentation] 雄ヤギ弓状核におけるキスペプチン、ニューロキニンBおよびダイノルフィンの発現 (2011)
  • Author(s): 本間玲実・若林嘉浩・山村 崇・坂本光平・大蔵 聡・森 裕司・岡村裕昭
  • Organizer: 第104回日本繁殖生物学会大会
  • Place of Presentation: 盛岡、いわて県民情報交流センター・アイーナ
• [Presentation] Neurokinin B受容体阻害剤が性腺刺激ホルモン放出ホルモン（GnRH）パルス産生機構の活動におよぼす影響 (2011)
  • Author(s): 山村 崇・若林嘉浩・大蔵 聡・本間玲実・坂本光平・森 裕司・岡村裕昭
  • Organizer: 第104回日本繁殖生物学会大会
  • Place of Presentation: 盛岡、いわて県民情報交流センター・アイーナ
• [Presentation] Kisspeptin: a key molecule controlling the activity of the hypothalamo-pituitary-gonadal axis. (2011)
  • Author(s): Uenoyama, Y., Ohkura, S., Tsukamura, H. and Maeda, K.-I.
  • Organizer: Japan-Poland Joint Seminar: Cutting-edge reproductive physiology -from gamete to baby -(招待講演)
  • Place of Presentation: 盛岡、いわて県民情報交流センター・アイーナ
• [Presentation] Male kisspeptin neuronal network and its interaction with GnRH neurons in goats. (2011)
  • Author(s): Ohkura, S., Matsuyama, S., Mogi, K., Wakabayashi, Y., Mori, Y., Tsukamura, H., Maeda, K.-I., Ichikawa, M. and Okamura, H.
  • Organizer: The 2nd World Congress on Reproductive Biology
  • Place of Presentation: Cairns, Australia、Cairns Convention Centre
• [Presentation] Differential effects of continuous exposure to the investigational metastin/kisspeptin analog TAK-683 on pulsatile and surge mode secretion of luteinizing hormone in ovariectomized goats. (2011)
  • Author(s): Tanaka, T., Ohkura, S., Wakabayashi, Y., Tanaka, A., Kusaka, M. and Okamura, H.
  • Organizer: The 2nd World Congress on Reproductive Biology
  • Place of Presentation: Cairns, Australia、Cairns Convention Centre
• [Presentation] Neuroendocrine mechanisms regulating reproductive functions in domestic ruminants.
  • Author(s): Ohkura, S.
  • Organizer: National Seminar HPTI, PEI and PFI East Java 2014
  • Place of Presentation: Surabaya, Indonesia
  • Invited
• [Presentation] キスペプチンニューロンによるGnRHパルス/サージ発生制御機構.
  • Author(s): 束村博子・上野山賀久・冨川順子・大蔵 聡・井上直子・前多敬一郎
  • Organizer: 第85回日本内分泌学会学術総会
  • Place of Presentation: 愛知県名古屋市
  • Invited
• [Presentation] ニホンザルのサージ状黄体形成ホルモン (LH)分泌におけるキスペプチンニューロンの役割.
  • Author(s): 渡辺雄貴・上野山賀久・家田菜穂子・川原万季・高瀬健志・末富祐太・鈴木樹理・大蔵 聡・前多敬一郎・束村博子
  • Organizer: 第105回日本繁殖生物学会大会
  • Place of Presentation: 茨城県つくば市
• [Presentation] Kisspeptin neurons in the medial preoptic area of castrated male goats mediate the surge-like luteinizing hormone secretion induced by acute elevations in circulating estrogen.
  • Author(s): Nakatsukasa, K., Suetomi, Y., Naniwa, Y., Ito, D., Inoue, N., Wakabayashi, Y., Okamura, H., Maeda, K.-I., Uenoyama, Y., Tsukamura, H., Matsuda, F. and Ohkura, S.
  • Organizer: The 2nd World Conference on Kisspeptin Signaling in the Brain
  • Place of Presentation: Tokyo, Japan
• [Presentation] Involvement of kisspeptin neurons in the regulation of estrogen-induced luteinizing hormone surge in both sexes of the Japanese macaque (Macaca fuscata fuscata).
  • Author(s): Watanabe, Y., Uenoyama, Y., Ieda, N., Kawahara, M., Takase, K., Suetomi, Y., Suzuki, J., Ohkura, S., Maeda, K.-I. and Tsukamura, H.
  • Organizer: The 2nd World Conference on Kisspeptin Signaling in the Brain
  • Place of Presentation: Tokyo, Japan
• [Presentation] 雌雄ニホンザルにおいてエストロジェンはKISS1ニューロンの活性化を介して黄体形成ホルモンのサージ状分泌を誘起する.
  • Author(s): 渡辺雄貴・上野山賀久・家田菜穂子・川原万季・高瀬健志・末富祐太・鈴木樹理・大蔵 聡・前多敬一郎・束村博子
  • Organizer: 第17回日本生殖内分泌学会学術集会
  • Place of Presentation: 東京
• [Presentation] 去勢雄シバヤギ視索前野のキスペプチンニューロンは高濃度エストロジェンにより誘起されるサージLH分泌を仲介する.
  • Author(s): 末富祐太・中務桂佑・難波陽介・若林嘉浩・岡村裕昭・前多敬一郎・上野山賀久・束村博子・松田二子・大蔵 聡
  • Organizer: 日本畜産学会第116回大会
  • Place of Presentation: 広島県広島市
• [Presentation] Estrogen induces surge-like luteinizing hormone secretion in gonadectomized male and female goats: involvement of kisspeptin neurons in the medial preoptic area in both sexes.
  • Author(s): Ohkura, S., Nakatsukasa, K., Suetomi, Y., Naniwa, Y., Ito, D., Inoue, N., Wakabayashi, Y., Okamura, H., Maeda, K.-I., Uenoyama, Y., Tsukamura, H. and Matsuda, F.
  • Organizer: The 46th Annual Meeting of the Society for the Study of Reproduction
  • Place of Presentation: Montreal, Canada
• [Book] Chapter 14: Kisspeptin and GnRH pulse generation. In Kisspeptin Signaling in Reproductive Biology(Eds. A.S. Kauffman and J.T.Smith.) (2013)
  • Author(s): Okamura, H., Tsukamura, H., Ohkura, S., Uenoyama, Y., Wakabayashi, Y. and Maeda, K.-I
  • Publisher: Springer, Berlin
• [Book] 視床下部および下垂体ホルモン. 「繁殖生物学」, 日本繁殖生物学会編. (2013)
  • Author(s): 大蔵 聡
  • Publisher: インターズー, 東京.
• [Book] Kisspeptin Signaling in Reproductive Biology (2013)
  • Author(s): Okamura, H., Tsukamura, H., Ohkura, S., Uenoyama, Y., Wakabayashi, Y. and Maeda, K.-I.
  • Total Pages: 514
  • Publisher: Springer
• [Book] 繁殖生物学 (2013)
  • Author(s): 大蔵 聡
  • Total Pages: 328
  • Publisher: インターズー
• [Remarks]
  • URL: http://www.agr.nagoya-u.ac.jp/~laps/