Building transgenic tools in Acomys cahirinus, an emerging model for mammalian regenerative biology and healthy aging

项目摘要 20世纪的许多重大生物学发现都是使用非常少的模式物种进行的。他们 选择的是历史易处理性，而不是与关键生物学问题相关的生物学属性， 与紧迫的全球卫生问题相关。然而，新的测序和基因组工程的出现 技术的发展使建立新的遗传模型成为可能。历史证明， 模式生物的研究是自我延续的：随着研究人员的成长，新的方法和 资源得到开发和共享，具体的知识体系和获得强大工具的机会， 对这些模式生物进行操作、观察和实验，进一步降低了进入的门槛， 循环可以重复（18）。在这里，我们建议为Acomys cahinirus一种新兴的转基因基础设施 成年哺乳动物非纤维化再生愈合和健康衰老的模型。我们提出了一个有条理的 为Acomys转基因提供了一个全面可行的方案。首先，我们提出了一种新的 利用我们已经产生的Acomys ES细胞和CRISPR 用荧光标记物标记。然后我们将致力于产生整个动物转基因Acomys动物 使用多种离体和原位方法。Acomys转基因将解开 Acomys的非凡再生生物学肯定会为人类健康带来新的治疗方法 和疾病

Project Summary Many of the major biological discoveries of the 20th century were made using very few model species. They were chosen for historical tractability, rather than biological attributes relevant to critical biological questions or relevance to pressing global health issues. However, the advent of new sequencing and genome engineering technologies makes establishment of new genetic models feasible. History has demonstrated that the success of model organisms is self-perpetuating: as the community of researchers grows, new methodologies and resources are developed and shared, and the body of specific knowledge and access to powerful tools to manipulate, observe and experiment upon these model organisms further lowers the bar to entry so that the cycle can repeat (18). Here we propose to develop transgenic infrastructure for Acomys cahinirus an emerging model of adult mammalian non-fibrotic regenerative healing and healthy aging. We have propose a methodical comprehensive and feasible plan to achieve transgenesis in Acomys. We first propose the generation of interspecies Mus musculus Acomys leveraging Acomys ES cells which we have generated and CRISPR tagged with a fluorescent marker. We will then work to generate whole animal transgenic Acomys animals using a variety of ex vivo and in situ methodologies. Acomys transgenesis will unlock the genetics of the extraordinary regenerative biology of Acomys certain to yield novel therapeutic approaches to human health and disease.