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.

项目概要 20 世纪的许多重大生物学发现都是利用极少数模式物种实现的。他们选择是为了历史的易处理性，而不是与关键生物学问题相关的生物学属性或与紧迫的全球健康问题的相关性。然而，新测序和基因组工程的出现技术使建立新的遗传模型变得可行。历史证明，成功模式生物的发展是自我延续的：随着研究人员群体的成长，新的方法和资源得到开发和共享，具体知识体系和强大工具的获取对这些模式生物进行操纵、观察和实验进一步降低了进入门槛，以便循环可以重复(18)。在这里，我们建议为 Acomys cahinirus 开发转基因基础设施，这是一种新兴的成年哺乳动物非纤维化再生愈合和健康衰老模型。我们提出了一个有条理的建议在 Acomys 中实现转基因的全面可行的计划。我们首先提出生成利用我们生成的 Acomys ES 细胞和 CRISPR 的种间 Mus musculus Acomys 用荧光标记进行标记。然后我们将致力于产生全动物转基因 Acomys 动物使用各种离体和原位方法。 Acomys 转基因将解锁 Acomys 非凡的再生生物学必将为人类健康带来新的治疗方法和疾病。