偽妊娠レシピエント雌マウスを効率よく用意する新手法を開発

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2026-07-06 基礎生物学研究所

自然科学研究機構 基礎生物学研究所の研究グループは、遺伝子改変マウスの作製に必要な偽妊娠レシピエント雌マウスを効率よく準備する新手法を開発した。従来は発情兆候を示す雌マウスを選んで精管切除済み雄と交配させていたが、本研究では、集団飼育により発情が抑制された雌マウスを対象とし、雄由来の匂い刺激によって発情を誘導・同期させるWhitten効果を利用した。発情兆候を示さない雌を雄と3日間同居させた結果、交配成立率は74~77%と、無作為交配群(53.5%)を大きく上回った。また、この方法で得た偽妊娠レシピエント雌マウスへ2細胞期胚を移植したところ、約90%の高い出産率が得られ、実用性が確認された。従来法と組み合わせることで、必要な雌マウスの飼育数を削減しながら安定的にレシピエントを確保できる可能性が示された。本成果は、動物実験における3R(代替・削減・改良)のうち、特に使用動物数の削減(Reduction)に貢献する技術として、生命科学研究の効率化と動物福祉の向上が期待される。

偽妊娠レシピエント雌マウスを効率よく用意する新手法を開発

<関連情報>

発情兆候を示さない雌マウス(Mus musculus)を用いた偽妊娠受容雌の準備:ウィッテン効果に基づく独自のアプローチの検討Preparation of Pseudopregnant Recipient Females Using Female Mice (Mus musculus) Showing Nonestrous Signs: Investigation of a Unique Approach Based on the Whitten Effect

Yuji Noguchi BS and Eiji Watanabe PhD
Journal of the American Association for Laboratory Animal Science  Published:01 May 2026
DOI:https://doi.org/10.30802/AALAS-JAALAS-25-131

Abstract

Availability of pseudopregnant recipient females is an essential component of embryo transfer in mice. However, conventional methods for sorting females based on estrous signs (proestrus or estrus) require maintaining a large stock of mice, thereby presenting challenges for animal welfare. Furthermore, these large numbers of female mice are often maintained in group housing due to space constraints; and this can induce the Lee-Boot effect, leading to decreased preparation efficiency. Therefore, this study examined a method for preparing pseudopregnant recipient females using mice showing nonestrous signs through a unique approach based on the Whitten effect. Female ICR mice exhibiting metestrus or diestrus characteristics were deliberately sorted and housed with vasectomized males for 3 consecutive days. The Lee-Boot effect was induced through group housing to increase the proportion of females showing nonestrous signs, followed by Whitten effect induction aimed at achieving successful copulation on day 3. Results demonstrated copulation success rates of 74.4% (CLEA Japan, n = 500) and 77.0% (Japan SLC, n = 200) on day 3, significantly higher than random mating controls during the same period (53.5%, Japan SLC, n = 101; December to May). Subsequent embryo transfers achieved high pregnancy rates of 93.1% and 89.6%, respectively. This approach demonstrated the feasibility of using mice showing nonestrous signs, previously overlooked in conventional methods, for preparing pseudopregnant recipient females. When combined with conventional methods, this approach expands the range of mice available for mating and potentially enables more efficient production of pseudopregnant recipient females while minimizing the total number of female mice required. This advancement aligns with the Replacement, Reduction, and Refinement (3Rs) principles of animal experimentation, particularly the reduction principle, and provides a practical strategy for laboratories seeking to perform embryo transfer procedures with smaller mouse numbers.

細胞遺伝子工学
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