Animal Core

动物核心（核心B）将监督本计划补助金的所有动物要求。核心B提供的狒狒模型被所有三个项目平等地使用。核心B的主要目标是在5年计划的每年提供20只妊娠狒狒进行剖腹产。为了实现这一目标，核心B将：（i）监督动物管理和饮食管理;（ii）启动育种方案;（iii）保存动物健康记录，包括饮食、形态学、产科和临床病史;（iv）安排和进行剖腹产手术;（v）管理组织收集过程、样本库存和组织共享计划，包括向项目和基因组学、表观基因组学和 蛋白质组学核心（核心C）。 核心B将包括一名PI（Dr. Nijland）、一名Co-PI（Dr. Nathanielsz）、三名动物技术员、一名数据 分析员和副奖PI Dr Laura考克斯（德克萨斯州生物医学研究所;提供访问动物和兽医服务的费用）。 为了实现其目标，核心B将为暴露于三种母体饮食的妊娠提供（每种饮食n=16）：（1）对照（CTR），（2）营养限制（MNR，从妊娠30天（d）开始为CTR的70%），以及 (3)干预（INT，MNR加CTR亮氨酸含量）。将在妊娠后半段的两个胎龄（140天和180天）（每个胎龄n=48;足月~ 185天）采集胎仔组织样本，以补充当前资助期（90天、120天和165天）研究的胎龄。我们知道MNR饮食与IUGR、胎儿循环必需氨基酸水平降低以及相对于CTR的一系列胎儿器官（包括胎盘、脑和肾）的结构和功能变化相关。狒狒和人类在生殖生理学上的惊人相似性和密切的进化关系，结合文献中关于狒狒代谢的大量信息，我们小组和SNPRC成员与非人类灵长类动物一起工作的集体经验，以及缺乏有关MNR对灵长类胎儿发育影响的机制的相关数据，证明了使用狒狒作为动物模型。

The Animal Core (Core B) will oversee all animal requirements of this Program Grant. The baboon model provided by Core B is used equally by all three Projects. The primary objective of Core B is to provide 20 pregnant baboons for C-Section in each year of the 5-year program. In order to achieve this objective, Core B will: (i) provide oversight of animal management and diet administration; (ii) initiate breeding protocols; (iii) maintain records of animal health including diet, morphometric, obstetric and clinical history; (iv) schedule and conduct C-Section surgeries; (v) manage the tissue collection process, sample inventory and the tissue sharing plan including distribution of samples to the Projects and the Genomics, Epigenomics and Proteomics Core (Core C). Core B will consist of a PI (Dr. Nijland), a Co-PI (Dr. Nathanielsz), three animal technicians, a Data Analyst and sub award PI Dr Laura Cox (Texas Biomedical Research Institute; providing fee for service access to the animals and veterinary services). To achieve its objectives, Core B will provide pregnancies exposed to three maternal diets (n=16 per diet): (1) control (CTR), (2) nutrient restricted (MNR, 70% of CTR starting at 30 days (d) of gestation), and (3) intervention (INT, MNR plus CTR leucine content). Fetal tissue samples will be obtained at two gestational ages in the second half of pregnancy, 140d and 180d (n=48 per age; term ~ 185d), chosen to complement the ages studied in the current funding period (90d, 120d and 165d). We know the MNR diet is associated with lUGR, reduced fetal circulating levels of essential amino acids, and structural and functional changes in a range of fetal organs including placenta, brain and kidney relative to CTR. The striking similarities in reproductive physiology and the close evolutionary relationship between baboons and humans, combined with the significant body of information on baboon metabolism available in the literature, the collective experience of our group and members of the SNPRC working with non-human primates, and the lack of relevant data on the mechanisms underlying the impact of MNR on primate fetal development proved a very strong justification for the use of the baboon as the animal model in this proposal.