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

– Red-NLAM – 减少实验动物模型的数量（通过提高人工繁殖率）

• 批准号: 720416
• 金额: $ 31.86万
• 依托单位: OSTARA BIOMEDICAL LIMITED
• 依托单位国家: 英国
• 项目类别: GRD Development of Prototype
• 财政年份: 2014
• 资助国家: 英国
• 起止时间: 2014 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=720416
• 关键词: Red; NLAM; reducing; numbers; laboratory

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.

根据英国内政部的数据，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，主要是小鼠和大鼠，已经彻底改变了我们对动物模型疾病过程的理解。转基因生物技术利用大量的动物：雌性和雄性产生用于基因操作的胚胎，雌性提供宿主子宫以支持胚胎的发育，而不育的雄性在受体雌性中诱导“假怀孕”。假妊娠是子宫接受移植胚胎的必要条件，通过培养雌性与绝育（不育）雄性交配来实现，其精液含有一系列活性蛋白质和其他因素。虽然我们不能取代女性的超排卵和怀孕，但我们已经在之前的概念证明研究中证明，输精管切除的男性可以完全取代。该项目的目标是开发一种原型阴道子宫托系统，以取代在诱导假妊娠中使用输精管切除术的男性，并提高宿主母亲的移植胚胎着床率。这些新型子宫托含有在小鼠精液中发现的物质，可以模拟精液的有益效果，而不需要对雄性输精管进行切除，也不需要大量雌性小鼠来产生足够的假怀孕小鼠。