“Red-NLAM” - reducing numbers in laboratory animal models (through improved artificial reproduction rates)

根据内政部的数据，仅在英国，2012年就有180万只老鼠被用于生产转基因老鼠的育种计划（约占所有用于研究的动物的48%）。转基因动物的创造，主要是老鼠和大鼠，彻底改变了我们对动物模型中疾病过程的理解。转基因生物技术利用大量的动物：雌性和雄性动物产生用于遗传操作的胚胎，雌性动物提供宿主子宫以支持胚胎的发育，不育的雄性动物在受体雌性动物中诱导“假孕”。假孕是子宫接受移植胚胎所必需的，通过将寄养雌性与切除卵巢（不育）的雄性交配来实现，雄性的精液含有一系列活跃的蛋白质和其他因子。虽然我们不能代替女性进行超数排卵和妊娠，但我们在之前的概念验证研究中已经证明，输精管切除的男性可以完全被移植。本项目的目标是开发一种原型阴道子宫托系统，该系统取代输精管切除的男性在诱导假孕和提高宿主母亲的转基因胚胎植入率中的使用。这些新型子宫托含有在小鼠精液中发现的物质，这些物质模拟精液的有益作用，而不需要切除输精管的雄性或大量雌性小鼠来产生足够的假孕小鼠。

In the UK alone, 1.8 million mice were used in breeding programmes for production oftransgenic mice in 2012, according to Home office figures (about 48% of all animal used inresearch).The creation of genetically modified animals, primarily mice and rats, has revolutionised ourunderstanding of disease processes in animal models. Transgenic biotechnologies utilise largenumbers of animals: females and males to generate embryos for genetic manipulation,females to provide a host uterus to support the development of embryos, and infertile males toinduce ‘pseudopregnancy’ in recipient females. Pseudopregnancy is necessary for the uterusto become receptive to transplanted embryos and is achieved by mating foster females with avasectomised (infertile) male, whose seminal fluid contains an active array of proteins andother factors. Whilst we can’t replace females for superovulation and pregnancy, we havedemonstrated in a previous Proof of Concept study that vasectomised males can be replacedaltogether.The objective of this project is the development of a prototype vaginal pessary system thatsupersedes the use of vasectomised males in the induction of pseudopregnancy and enhancestransgenic embryo implantation rates in the host mothers. These novel pessaries containsubstances that have been identified in mouse seminal fluid that mimic the beneficial effectsof semen without the need for vasectomised males or the large numbers of female miceneeded to produce enough pseudopregnant mice.