Development of an Economic Process to Store and Recover Homozygous Mouse Strains

开发储存和恢复纯合小鼠品系的经济流程

• 批准号: 7882266
• 负责人: Michael Van Wiles
• 金额: $ 26.1万
• 依托单位: JACKSON LABORATORY
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-07-01 至 2012-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7882266
• 关键词: Accounting; Address; Affect; Animals; Archives; Artificial Insemination; Assisted Reproductive Technology; Birth; Breeding; Characteristics; Charge; Communities; Complex; Country; Cryopreservation; Economic Development; Economics; Embryo; Female; Fertilization in Vitro; Freezing; Genes; Genetic; Genotype; Growth; Human; Human Genome; Insemination; Kinetics; Laboratories; Laboratory mice; Life; Link; Maintenance; Methods; Modification; Mouse Strains; Mus; Oocytes; Operative Surgical Procedures; Ovarian; Ovary; Ovulation; Process; Productivity; Public Health; Recovery; Repository Operations; Research; Research Personnel; Resources; Retrieval; Risk; Scheme; Study models; Technology; Time; Transplant Recipients; Transplantation; cost; cost effective; egg; exhaust; human disease; innovation; method development; mouse genome; mouse model; novel; novel strategies; offspring; public health relevance; reconstitution; repository; sperm cell

DESCRIPTION (provided by applicant): The laboratory mouse is a key model for the study of human diseases mainly because the mouse and human genomes are strikingly similar. The ability to modify the mouse genome by disrupting genes or inserting human genes allows researchers to develop highly specific strains for study and has led to an exponential growth in the number and complexity of strains. Creating these strains is not trivial and complex strains must be kept homozygous through breeding closely related animals; otherwise, non-linked loci will segregate among the offspring and strain characteristics will be disrupted. Cryopreservation is used to store strains that are not actively being studied and to protect strains if the breeding colony is lost. However, during cryopreservation or recovery wild type egg donors are used and the homozygosity of the strain is not maintained. In addition, the available methods to cryopreserve and store strains are expensive, time consuming, and require many animals. There is a pressing need to develop a method for cryopreserving strains in a manner which retains the original genotype. The method must be quick, economic, and use few animals. A combination of routine and novel assisted reproductive technologies will be developed to archive and recover homozygous strains. These processes will use 3-5 times fewer resources compared to current embryo cryopreservation methods. Homozygous strains will be archived by cryopreserving both sperm and ovaries. Strains will then be reconstituted using a combination of surgical artificial insemination (surgical AI) and ovarian transplant. Additionally, serial ovarian transplant and surgical oocyte retrieval methods will be explored as alternative methods to recover cryopreserved sperm and ovaries. The reconstitution of strains from the freezer will be developed to reflect the diverse needs of the scientific community and will provide: i) a fast and low cost recovery, delivering 2-3 homozygous breeding pairs, and ii) a moderately fast, higher cost recovery, delivering =10 homozygous breeding pairs. PUBLIC HEALTH RELEVANCE (provided by applicant): Assisted Reproductive Technologies now account for more than 5% of all births in the first world countries. A major limitation to human IVF is the paucity of oocytes. Our research will help understand and, hopefully, increase the oocytes productivity in humans.

描述（由申请人提供）：实验室小鼠是研究人类疾病的关键模型，主要是因为小鼠和人类基因组非常相似。通过破坏基因或插入人类基因来修饰小鼠基因组的能力使研究人员可以为研究开发高度特异性的菌​​株，并导致菌株数量和复杂性的指数增长。产生这些菌株并不是微不足道的，必须通过繁殖紧密相关的动物来保持纯合的复杂菌株。否则，在后代和应变特征之间将分离非连接的基因座将被破坏。冷冻保存用于存储未积极研究的菌株，并在繁殖菌落丢失时保护菌株。但是，在冷冻保存或恢复期间，使用了野生型卵子供体，并且未保持菌株的纯合性。此外，冷冻水果和商店应变的可用方法昂贵，耗时，需要许多动物。迫切需要以一种保留原始基因型的方式来开发一种冷冻菌株的方法。该方法必须快速，经济，并且使用很少的动物。将开发常规和新型辅助生殖技术的结合，以存档和恢复纯合子菌株。与当前的胚胎冷冻保存方法相比，这些过程的资源将减少3-5倍。纯合子菌株将通过冷冻水平来存档精子和卵巢。然后，将使用手术人工授精（手术AI）和卵巢移植的组合来重组菌株。此外，将探索连续卵巢移植和手术卵母细胞检索方法作为回收冷冻保存精子和卵巢的替代方法。将开发从冰箱中的菌株重建，以反映科学界的各种需求，并将提供：i）快速，低成本恢复，提供2-3个纯合育种对，ii）中等快速，更高的成本恢复，提供= 10个纯合育种对。 公共卫生相关性（由申请人提供）：辅助生殖技术现在占第一世界国家所有出生的5％以上。人IVF的主要局限性是卵母细胞的缺乏。我们的研究将有助于理解并希望提高人类的卵母细胞生产力。