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

在 Acomys cahirinus 中构建转基因工具，这是一种哺乳动物再生生物学和健康衰老的新兴模型

基本信息

批准号：
10327728
负责人：
Kathleen Joyce Millen
金额：
$ 23.56万
依托单位：
SEATTLE CHILDREN'S HOSPITAL
依托单位国家：
美国
项目类别：
财政年份：
2021
资助国家：
美国
起止时间：
2021-01-15 至 2023-12-31
项目状态：
已结题

项目摘要

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.

项目摘要 20世纪的许多重大生物学发现都是用极少的模式物种完成的。他们而不是与关键的生物学问题相关的生物学属性或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使建立新的遗传模型成为可能。历史已经证明，成功模型生物的发展是自我延续的：随着研究人员社区的发展，新的方法和资源是开发和共享的，而特定知识的主体和访问强大的工具来对这些模型生物进行操作、观察和实验进一步降低了进入门槛，从而使循环可以重复(18)。在这里，我们建议为正在出现的一种名叫Acomys cahinirus的植物开发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模型。我们已经提出了一个有条不紊的在Acomys实现转基因的全面可行的计划。我们首先建议产生利用我们培育的Acomys ES细胞和CRISPR进行种间小鼠的研究用荧光记号笔标记的。然后我们将致力于培育出全动物转基因的Acomys动物使用各种体外和原位方法。阿科姆公司的转基因将解开 Acomys非凡的再生生物学肯定会为人类健康带来新的治疗方法和疾病。