Equipment and Instrument Infrastructure Improvement for the MMRRC at UC Davis

加州大学戴维斯分校MMRRC的设备和仪器基础设施改进 摘要和工作范围 加州大学戴维斯分校(MMRRC)突变老鼠资源和研究中心(MMRRC)很高兴 提交本行政补充文件，提供最长1年的支持，以回应ORIP参与PA- 20-272，“对现有NIH补助金和合作协议的行政补充”，具体涉及 支持设施的改建和翻新(A&R)和/或购买仪器和设备 支持非艾滋病研究。本申请建议购买和安装设备和 确保和提高畜牧、生产和生产的质量、严格性和能力的仪器 MMRRC维护和分布的突变小鼠品系的表型鉴定。具体地说，此应用程序 要求资金将我们的MMRRC设施的运营、适用性、功能和能力提高1) 取代损坏和不可修复的冷冻恢复和分析仪器，并实现异地储存 MMRRC种质冷冻库，2)升级现有的动物转运站，以显著改善 MMRRC小鼠品系的无特定病原体(SPF)饲养质量，以及3)获得和 纳入专门的仪器和设备，以促进新的和实施改进 肌肉骨骼、肺和行为表型鉴定能力，为研究增加实质性内容 正直、严谨和可重复性。这个项目的资金将实现5件事。首先，它将显著地 提高冷冻复苏和试管受精效率，从而加快可用性，促进快速 向提出请求的调查人员传播老鼠线。第二，它将加快对 MMRRC小鼠品系的生殖生物学，为用户提供关于精子的有价值的信息 表型，并确保从冷冻档案中回收。第三，它将极大地提高 为MMRRC小鼠提供饲养和保健，并提供过敏原控制，以保护间隔菌工作人员。 第四，它将实现可以在所有MMRRC小鼠上进行的表型验证和深度分析 菌株，从而直接回应用户对更广泛和全面的检测和分析的要求。 第五，它将提高生产和表型活动的严密性、再现性和透明度，进一步 支持MMRRC为获得全国机构认可的供应商地位所作的努力。 总之，这些升级将显著增强我们满足MMRRC日益增长的期望的能力 为客户提供全面验证的小鼠模型，并优化生产和表型服务。 此外，由于这些升级是特定于MMRRC项目的，它们超出了 加州大学戴维斯分校的基本运营和维护。本补编的总体结果将是 通过改进和扩大MMRRC的业务，对MMRRC的运作产生持续而有力的影响 能够更专业地维护、管理和表征转基因小鼠品系和满足 美国国立卫生研究院资助研究的国家生物医学研究界的需求。通过这样做，这就是 补充将为整个研究界提供持续的好处，并对 美国国立卫生研究院资助的研究。父母同行评审的NIH资助赠款(U42OD012210)一直具有竞争力 续签(自2020年1月1日起)，为期5年。请拨剩余费用预算478 325美元(总费用) 本赠款年度(截至2024年1月31日)的月份不到年度直接成本预算总额的一半 家长拨款。拟议的所有活动都属于父裁决的范围，其中包括存档、 表型分型，并分发研究人员来源的和中心生产的突变小鼠品系。

Equipment and Instrument Infrastructure Improvement for the MMRRC at UC Davis ABSTRACT & SCOPE OF WORK The Mutant Mouse Resource and Research Center at the University of California, Davis (MMRRC) is pleased to submit this administrative supplement for up to 1 year of support in response to ORIP's participation in PA- 20-272, “Administrative Supplements to Existing NIH Grants and Cooperative Agreements” specifically related to support alterations and renovations (A&R) of facilities and/or purchase of instruments and equipment in support of non-AIDS research. This application proposes the purchase and installation of equipment and instrumentation to ensure and increase the quality, rigor, and capability of husbandry, production, and phenotyping of mutant mouse lines maintained and distributed by the MMRRC. Specifically, this application requests funds to improve operations, serviceability, functionality and capability of our MMRRC facilities by 1) replacing broken and irreparable cryorecovery and analytical instrumentation and to enable off-site storage of the MMRRC germplasm cryoarchive, 2) upgrading existing animal transfer stations to substantially improve the quality of specific pathogen-free (SPF) husbandry for MMRRC mouse strains, and 3) obtaining and incorporating specialized instrumentation and equipment to facilitate new and implement improvements in musculoskeletal, pulmonary, and behavioral phenotyping capabilities that add substantively to research integrity, rigor, and reproducibility. Funding of this project will accomplish 5 things. First, it will significantly improve cryorecovery and IVF efficiency, thus accelerating the availability and facilitating the rapid dissemination of mouse lines to requesting investigators. Second, it will expedite quality control analysis of the reproductive biology of MMRRC mouse strains, adding valuable information to users regarding sperm phenotype and ensuring their recovery from the cryoarchive. Third, it will dramatically improve the quality of husbandry and health care for MMRRC mice and provide allergen containment to protect vivarium staff. Fourth, it will enable the validation and depth of phenotyping that can be conducted on all MMRRC mouse strains, thus directly responding to users' requests for more extensive and comprehensive testing and analysis. Fifth, it will improve rigor, reproducibility, and transparency in production and phenotyping activities, further supporting efforts by the MMRRC to achieve approved vendor status by institutions across the country. Together, these upgrades will significantly enhance our ability to meet the increased expectations of MMRRC clientele for fully comprehensively validated mouse models and optimize production and phenotyping services. Further, because these upgrades are MMRRC-project specific, they are beyond the support provided by the UC Davis campus for basic operations and maintenance. The overall outcome of this supplement will be to exert a sustained and powerful influence on operations of the MMRRC by improving and expanding its capability to more expertly maintain, manage, and characterize genetically-modified mouse strains and meet the needs of the national biomedical research community conducting NIH-funded research. By doing so, this supplement will provide a sustained benefit to the overall research community and have a positive impact on NIH-funded research. The parent peer-reviewed NIH funded grant (U42OD012210) has been competitively renewed (as of January 1, 2020) for 5 years. A budget of $478,325 (total costs) requested for the remaining months of the current grant year (until January 31, 2024) is less than half the annual total direct cost budget of the parent grant. The proposed activities all fall within the scope of the parent award, which includes archiving, phenotyping, and distributing investigator-derived and Center-produced mutant mouse lines.