ANIMAL AND PATHOLOGY CORE

动物和病理学核心

• 批准号: 7232318
• 负责人: HARRY VAN STEEG
• 金额: $ 31.39万
• 依托单位: BUCK INSTITUTE FOR RESEARCH ON AGING
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/7232318
• 关键词: DNA damage; DNA repair; aging; animal colony; biomedical facility; cell line; cell senescence; gene mutation; genetic strain; genetically modified animals; germ free condition; histopathology; laboratory mouse; oxidative stress

The Animal Research Facility of the National Institute of Public Health and the Environment (RIVM, The Netherlands) has successfully conducted several longevity and cross sectional studies with mice having a defect in DNA repair and/or RNA transcription. Some of these mouse strains showed phenotypes of accelerated aging. As part of the present program renewal application the animal and pathology core will continue to conduct those studies, but will now have a more specific focus (based on the results obtained in the previous grant period) and will include intervention studies. On the basis of results that will come out of the 4 projects, strategies will be developed to decrease oxidative DNA damage (considered as a main driving force in aging) in the mouse, using various modes of antioxidant and/or genome maintenance interventions. Overall, the specific aims of the animal/pathology core are: 1) to ensure uniformity and homogeneity of animals and the environment in which the animals will be housed; consequently the animals are (or will be) backcrossed into the same genetic C57BL/6 background. 2) to ensure that the animals are raised in a pathogen free environment; 3) to facilitate the sharing of animals and tissues or cells from them between the individual investigators; 4) to conduct longevity and/or cross sectional studies with Xpc, Erccl, Ku70, Ku80, Rad54/54B mice or mouse strains with combined DNA repair deficiencies, like Ttd/Ku80 (in total 15 studies); 5) to conduct life extension and exposure studies with Erccl mice (7 studies); 6) to conduct full histopathology on all animals from the longevity studies and if necessary also on mice from the cross sectional studies; 7) to set up strategies to include new mouse models in the life span and intervention studies on the basis of the results obtained in the 4 projects To make mutagenesis studies possible, all transgenic mouse lines will be crossed with lacZ containing pUR288 transgenic mice (see also studies as described in project 2).

美国国家公共卫生与环境研究所（荷兰RIVM）的动物研究机构成功地进行了多次寿命和横断面研究，其中具有DNA修复和/或RNA转录缺陷的小鼠。其中一些小鼠菌株显示出加速衰老的表型。作为本计划更新应用的一部分，动物和病理学核心将继续进行这些研究，但现在将更具体的重点（基于上一个赠款期间获得的结果），并将包括干预研究。根据这四个项目将产生的结果，将采用各种抗氧化剂和/或基因组维持干预措施，制定策略以减少小鼠中氧化性DNA损伤（被认为是衰老的主要驱动力）。总体而言，动物/病理核心的具体目的是： 1）确保动物的统一性和同质性以及动物所在的环境；因此，这些动物（或将）被反向跨入相同的遗传C57BL/6背景。 2）确保在无病原体环境中饲养动物； 3）促进单个研究人员之间的动物和组织或细胞的共享； 4）使用XPC，ERCCL，KU70，KU80，RAD54/54B小鼠或小鼠菌株进行寿命和/或横截面研究，具有DNA修复缺陷，例如TTD/KU80（总计15个研究）； 5）用ERCCL小鼠进行生命延长和暴露研究（7个研究）； 6）对寿命研究的所有动物进行全面组织病理学，并在必要时对横截面研究的小鼠进行。 7）制定策略，根据在4个项目中获得的结果中包括新的鼠标模型和干预研究 为了使诱变研究成为可能，所有转基因小鼠系都将与含有PUR288转基因小鼠的LACZ交叉（另请参见项目2中所述的研究）。