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的突变小鼠资源和研究中心（MMRRC）很高兴 提交此行政补充，以获得长达1年的支持，以响应ORIP参与PA- 20-272，“对现有NIH赠款和合作协议的行政补充”特别涉及 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， 仪器，以确保和提高质量，严谨性和畜牧业，生产， 由MMRRC维护和分发的突变小鼠品系的表型分析。具体而言，该应用程序 要求资金，以改善我们的MMRRC设施的运营，适用性，功能和能力1） 更换损坏和无法修复的冷冻回收和分析仪器， MMRRC种质冷冻库，2）升级现有的动物转移站， MMRRC小鼠品系的无特定病原体（SPF）饲养质量，和3）获得和 采用专门的仪器和设备，以促进新的和实施的改进， 肌肉骨骼、肺部和行为表型分析能力，为研究提供了实质性的帮助 完整性、严谨性和可重复性。该项目的资金将完成五件事。首先，它将大大 提高冷冻复苏和IVF效率，从而加快可用性并促进快速 向提出请求的研究者分发小鼠品系。第二，它将加快质量控制分析， MMRRC小鼠品系的生殖生物学，为用户提供有关精子的有价值信息 表型，并确保其恢复从冷冻档案。第三，它将大大提高质量， 饲养和保健MMRRC小鼠，并提供过敏原遏制，以保护动物园工作人员。 第四，它将使得能够对所有MMRRC小鼠进行表型分型的验证和深度 因此，直接响应用户对更广泛和全面的测试和分析的要求。 第五，它将提高生产和表型分析活动的严谨性、可重复性和透明度， 支持小额供资和资源中心努力使全国各机构获得核准的供应商地位。 总之，这些升级将大大提高我们的能力，以满足MMRRC增加的期望 为客户提供全面验证的小鼠模型，并优化生产和表型分析服务。 此外，由于这些升级是MMRRC项目特定的，它们超出了 加州大学戴维斯分校的基本操作和维护。这一补充的总体结果将是 通过改善和扩大其对MMRRC业务的持续和强大的影响， 能够更专业地维护、管理和表征转基因小鼠品系， 国家生物医学研究社区进行NIH资助的研究的需求。通过这样做， 补充将为整个研究界提供持续的利益，并对 NIH资助的研究。父母同行评审的NIH资助的赠款（U42 OD 012210）已竞争性 续期（自2020年1月1日起）5年。为其余项目请拨预算478 325美元（费用总额） 本补助年度（截至2024年1月31日）的30个月不到年度直接成本预算总额的一半。 家长补助金拟议的活动都属于母奖的范围，其中包括存档， 表型分析，以及分配突变体衍生的和中心产生的突变小鼠品系。

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.