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.