Genetic Modification to Harness the Regenerative Power of the African Spiny Mouse

项目摘要 再生医学的一个基本目标是取代受损的纤维化和瘢痕形成。 具有功能组织的哺乳动物组织。到目前为止，在实现以下目标方面进展甚微 这一目标是因为缺乏一种成年哺乳动物模型系统来证明 而受损的哺乳动物皮肤的典型反应是形成无毛的， 胶原性疤痕。然而，最近的研究表明，非洲刺鼠(Acomys)，以下 全层皮肤去除，可再生去除的所有组织：表皮，毛发， 肉脂瘤的皮脂腺、竖毛肌、真皮和骨骼肌， 全都没有疤痕。在我们到目前为止的实验中，描述了 再生阿科姆的皮肤伤口和疤痕小鼠的皮肤伤口，我们已经确定了许多 分子上的差异，但我们还不知道究竟是什么导致了再生 对伤痕累累。 揭示Acomys这种非凡的再生能力背后的分子机制 对于正常的组织，科学界需要一种方法来修改动物的基因。例如, 我们之前发现，Acomys的皮肤再生中，III型胶原含量特别丰富， 而MUS在创面瘢痕形成过程中表现出更高的I型和III型胶原比例1。 然而，我们不知道这种丰富的III型胶原是如何在更高的 Acomys的再生能力。在本提案中，我们将敲除COL3a1基因 Acomys成纤维细胞以及整个动物作为研究其作用的样本 特定的基因在动物的伤口修复能力较高。建立高效的社会保障体系 Acomys的基因编辑方法将为哺乳动物开辟一条革命性的新途径 再生研究。

PROJECT ABSTRACT A fundamental goal of regenerative medicine is to replace fibrosis and scarring in damaged mammalian tissues with functional tissue. Thus far there has been very little progress towards this goal because of a lack of an adult mammalian model system that demonstrates functional regeneration, and instead the typical response of damaged mammalian skin is to form a hairless, collagenous scar. However, recent studies revealed that African spiny mouse (Acomys), following full thickness skin removal, can regenerate all the tissues removed: the epidermis, hair, sebaceous glands, erector pili muscles, dermis and skeletal muscle of the panniculus carnosus, all without scarring. In our experiments to date characterizing the differences between regenerating Acomys skin wounds and scarring Mus skin wounds, we have identified many molecular differences but we have no real handle on what exactly are responsible for regeneration vs scarring. To reveal molecular mechanisms underlying this remarkable capacity of Acomys to regenerate normal tissue, the scientific community needs a way to modify genes in the animals. For instance, we previously identified that collagen type III is particularly abundant in Acomys skin regeneration, whereas Mus exhibits a much higher ratio of collagen type I to type III during wound scarring1. However, we do not know that how this abundant collagen type III plays a role in a higher regenerative capacity of Acomys. In the present proposal, we will knockout the Col3a1 gene within Acomys fibroblasts as well as the whole animals as an exemplar with which to study the role of specific genes in higher wound repair capacity of the animal. The establishment of an efficient gene editing method with Acomys will open a revolutionary new avenue for mammalian regeneration research.