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

Kana IKEGAMI; Teppei GOTO; Sho NAKAMURA; Youki WATANABE; Arisa SUGIMOTO; Sutisa MAJARUNE; Kei HORIHATA; Mayuko NAGAE; Junko TOMIKAWA; Takuya IMAMURA; Makoto SANBO; Masumi HIRABAYASHI; Naoko INOUE; Kei-ichiro MAEDA; Hiroko TSUKAMURA; Yoshihisa UENOYAMA

doi:10.1262/jrd.2020-026

Original Article

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

Kana IKEGAMI, Teppei GOTO, Sho NAKAMURA, Youki WATANABE, Arisa SUGIMOTO, Sutisa MAJARUNE, Kei HORIHATA, Mayuko NAGAE, Junko TOMIKAWA, Takuya IMAMURA, Makoto SANBO, Masumi HIRABAYASHI, Naoko INOUE, Kei-ichiro MAEDA, Hiroko TSUKAMURA, Yoshihisa UENOYAMA

Author information

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

Keywords: Cre/loxP system, Gonadotropin, Kisspeptin, Pubertal failure

JOURNAL OPEN ACCESS

2020 Volume 66 Issue 4 Pages 359-367

DOI https://doi.org/10.1262/jrd.2020-026

Browse “Advance online publication” version

Details

Abstract

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.

Fullsize Image

Corresponding author