A non-surgical embryo transfer (NSET) device for producing gene-modified mice

描述（由申请方提供）：在研究中使用研究动物对于疫苗的开发和大多数人类疾病的研究至关重要。现代啮齿类动物研究越来越强大，能够操纵小鼠和大鼠的基因组，使它们接近模拟复杂的人类疾病，如阿尔茨海默氏症和关节炎。产生转基因小鼠和大鼠，需要将研究人员操纵的胚胎转移到受体雌性小鼠中，在那里它们可以完成发育。到目前为止，这些转移需要将胚胎植入子宫的外科手术。最近，已经开发了一种装置，该装置使得这些胚胎移植能够在没有手术的情况下进行，这消除了手术后的恢复期，从而减少了动物的疼痛。该提议通过建立用于胚胎移植的最佳年龄和小鼠品系（目标1），确定胚胎干细胞是否可以用该装置有效地和高效地转移（目标2），确定该装置是否用于人工授精（目标3），直接可视化子宫内的器械，这可能会改进设计（目标4），并量化与外科手术相关的应力测量，以支持该手术在研究界的广泛采用（目标5）。该项目的主要目标是产生数据，证明这种胚胎移植设备的有效性，从而使研究人员能够用同样有效的非手术方法取代手术程序。证明这种非手术转移方法在一系列条件下是有效的，将扩大其在这一应用范围内的使用，从而最大限度地提高其影响，使研究人员能够改进和减少在小鼠中进行的外科手术的数量。 公共卫生相关性：动物在研究中的使用对于生物医学研究至关重要，并且随着基因工程小鼠用于研究的能力的发展;这些动物变得更加重要，因为它们可以被修改以模仿大多数人类疾病。小鼠的基因工程需要，作为许多其他事情之一，能够将胚胎移植到小鼠体内，在那里它们完成发育。该项目支持进一步开发一种设备，使这些胚胎移植能够在不手术的情况下进行，从而大大减少这些研究动物经历的疼痛类别，从而支持生物医学的进步。

DESCRIPTION (provided by applicant): The use of research animals in research has been essential to development of vaccines and study of most human diseases. Modern rodent research is increasingly powerful with the ability to manipulate the genomes of mice and rats such that they closely mimic complex human diseases such as Alzheimer's and artherosclerosis. Generating transgenic mice and rats, requires that embryos that are manipulated by researchers be transferred into recipient female mice where they can complete their development. Up to this point, these transfers have required surgical procedures in which the embryo is implanted into the uterus. Recently, a device has been developed that enables these embryo transfers to be performed without surgery which eliminates the post-operative recovery period thereby reducing pain of the animals. This proposal investigates and expands upon the utility of this embryo transfer device by establishing the optimal ages and mouse strains for embryo transfer (Aim 1), determining whether embryonic stem cells can be effectively and efficiently transferred with this device (Aim 2), determining whether the device is useful for artificial inseminations (Aim 3), directly visualizing the device in the uterus which may enable design improvements (Aim 4) and quantifying measures of stress relative to surgical procedures to support widespread adoption of this procedure in the research community (Aim 5). The primary project objective is to produce data that will prove the efficacy of this embryo transfer device and thereby enable researchers to replace surgical procedures with a non-surgical method that is equally effective. Proving that this non-surgical transfer method is effective under a range of conditions will expand its use over this range of applications and thereby maximize its impact in enabling researchers to refine and reduce the number of surgical procedures performed in mice. PUBLIC HEALTH RELEVANCE: Animal use in research is essential for biomedical research and with the developing abilities to genetically engineer mice for research; these animals are becoming even more important as they can be modified to mimic most human diseases. Genetic engineering of mice requires, as one of many other things, the ability to transfer embryos into mice where they complete their development. This project supports further development of a device that enables these embryo transfers to be performed without surgery and therefore greatly reduces the pain category that these research animals experience and thereby supports progress in biomedicine.