Conditional kisspeptin neuron-specific <i>Kiss1</i> knockout with newly generated <i>Kiss1</i>-floxed and <i>Kiss1</i>-Cre mice replicates a hypogonadal phenotype of global <i>Kiss1</i> knockout mice

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  • IKEGAMI Kana
    Graduate School of Bioagricultural Sciences, Nagoya University, Nagoya 464-8601, Japan
  • GOTO Teppei
    Graduate School of Bioagricultural Sciences, Nagoya University, Nagoya 464-8601, Japan Center for Genetic Analysis of Behavior, National Institute for Physiological Sciences, Okazaki 444-8585, Japan
  • NAKAMURA Sho
    Graduate School of Agricultural and Life Sciences, The University of Tokyo, Tokyo 113-8657, Japan
  • WATANABE Youki
    Graduate School of Bioagricultural Sciences, Nagoya University, Nagoya 464-8601, Japan
  • SUGIMOTO Arisa
    Graduate School of Bioagricultural Sciences, Nagoya University, Nagoya 464-8601, Japan
  • MAJARUNE Sutisa
    Graduate School of Bioagricultural Sciences, Nagoya University, Nagoya 464-8601, Japan
  • HORIHATA Kei
    Graduate School of Bioagricultural Sciences, Nagoya University, Nagoya 464-8601, Japan
  • NAGAE Mayuko
    Graduate School of Bioagricultural Sciences, Nagoya University, Nagoya 464-8601, Japan
  • TOMIKAWA Junko
    Graduate School of Bioagricultural Sciences, Nagoya University, Nagoya 464-8601, Japan
  • IMAMURA Takuya
    Graduate School of Integrated Sciences for Life, Hiroshima University, Hiroshima 739-8526, Japan
  • SANBO Makoto
    Center for Genetic Analysis of Behavior, National Institute for Physiological Sciences, Okazaki 444-8585, Japan
  • HIRABAYASHI Masumi
    Center for Genetic Analysis of Behavior, National Institute for Physiological Sciences, Okazaki 444-8585, Japan
  • INOUE Naoko
    Graduate School of Bioagricultural Sciences, Nagoya University, Nagoya 464-8601, Japan
  • MAEDA Kei-ichiro
    Graduate School of Agricultural and Life Sciences, The University of Tokyo, Tokyo 113-8657, Japan
  • TSUKAMURA Hiroko
    Graduate School of Bioagricultural Sciences, Nagoya University, Nagoya 464-8601, Japan
  • UENOYAMA Yoshihisa
    Graduate School of Bioagricultural Sciences, Nagoya University, Nagoya 464-8601, Japan

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  • Conditional kisspeptin neuron-specific Kiss1 knockout with newly generated Kiss1-floxed and Kiss1-Cre mice replicates a hypogonadal phenotype of global Kiss1 knockout mice

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<p> The present study aimed to evaluate whether novel conditional kisspeptin neuron-specific Kiss1 knockout (KO) mice utilizing the Cre-loxP system could recapitulate the infertility of global Kiss1 KO models, thereby providing further evidence for the fundamental role of hypothalamic kisspeptin neurons in regulating mammalian reproduction. We generated Kiss1-floxed mice and hypothalamic kisspeptin neuron-specific Cre-expressing transgenic mice and then crossed these two lines. The conditional Kiss1 KO mice showed pubertal failure along with a suppression of gonadotropin secretion and ovarian atrophy. These results indicate that newly-created hypothalamic Kiss1 KO mice obtained by the Cre-loxP system recapitulated the infertility of global Kiss1 KO models, suggesting that hypothalamic kisspeptin, but not peripheral kisspeptin, is critical for reproduction. Importantly, these Kiss1-floxed mice are now available and will be a valuable tool for detailed analyses of roles of each population of kisspeptin neurons in the brain and peripheral kisspeptin-producing cells by the spatiotemporal-specific manipulation of Cre expression.</p>

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