Animal Core

动物核心(核心B)将监督本计划拨款的所有动物要求。所有三个项目都平等地使用了核心B提供的狒狒模型。核心B的主要目标是在5年计划的每一年提供20只怀孕的鸵鸟进行剖腹产。为了实现这一目标，核心B将：(1)监督动物管理和饮食管理；(2)启动繁殖规程；(3)保存动物健康记录，包括饮食、形态测量、产科和临床病史；(4)安排和进行剖腹产手术；(5)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将由一名PI(Nijland博士)、一名共同PI(Nathanielsz博士)、三名动物技术员、一名数据 分析师和分奖派劳拉·考克斯博士(德克萨斯生物医学研究所；提供动物服务和兽医服务的费用)。 为了实现其目标，核心B将向孕妇提供三种饮食(每种饮食n=16)：(1)对照(CTR)，(2)营养限制(MNR，从怀孕30天(D)开始的CTR的70%)，以及 (3)干预(INT、MNR+CTR亮氨酸含量)。胎儿组织样本将在妊娠后半期的两个孕周，即140d和180d(n=48/a；孕期~185d)采集，以补充当前资助期(90d、120d和165d)研究的年龄。我们知道，与CTR相比，MNR饮食与LUGR、胎儿循环必需氨基酸水平降低以及包括胎盘、脑和肾脏在内的一系列胎儿器官的结构和功能变化有关。在生殖生理学和人类之间的密切进化关系上的惊人相似性，再加上文献中大量关于狒狒新陈代谢的信息，我们小组和SNPRC成员与非人类灵长类动物合作的集体经验，以及关于MNR对灵长类胚胎发育影响的潜在机制的相关数据的缺乏，证明了在本提案中使用狒狒作为动物模型的非常有力的理由。

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.