PRODUCTION OF PEDIGREED SPF RHESUS MACAQUES: HIV ANIMAL MODELS

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 描述(由申请人提供)： 这项建议的目标是扩大印度血统恒河猴的生产，这些恒河猴对7种持久病毒没有特定病原体(SPF)，包括恒河猴免疫缺陷病毒(SIV)、D型逆转录病毒(SRV)、恒河猴T淋巴细胞嗜毒病毒(STLV)、脑炎疱疹病毒1(B病毒)、恒河猴泡沫病毒(SFV)、恒河猴巨细胞病毒(RhCMV)和恒河猴狂犬病病毒(RRV)。这项拟议的扩展将用于生产用于艾滋病相关研究的SPF动物，并建立一个具有已知系谱和明确MHC基因类型的印度原产猕猴的长期SPF繁育群体。为了达到这些目标，我们将通过哺育新生儿的方式，从传统的、非SPF的印度恒河猴繁育群中获得SPF后代。此外，我们还将通过自然繁殖和社会群体中的母亲饲养，扩大现有的印度起源群体，即对5种持久性病毒(SIV、SRV、STLV、SFV、B病毒)的SPF。一个扩展的MHC分型程序，包括额外的微卫星座位、I类等位基因和II类基因，将用于鉴定后代和他们的父母。这种扩大的MHC分型将允许识别和定义免疫反应基因类型，并将允许选择育种生产具有特定遗传特征的动物。我们还建议收集在苗圃饲养和母亲饲养的SPF猕猴队列中主要淋巴细胞亚群随年龄变化的纵向数据。年龄特定的参考范围是从正常、健康的SPF-猕猴发展而来的，对于更充分地了解和利用猕猴模型系统，以及提供能够更准确地解释在艾滋病和其他传染病和免疫性疾病中观察到的淋巴细胞亚群表型变化的比较数据是必不可少的。作为这笔赠款的一部分，培育的恒河猴将为艾滋病相关研究提供宝贵的资源。这些动物将用于与疫苗开发和抗病毒治疗相关的研究。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. DESCRIPTION (provided by applicant): The goal of this proposal is to expand the production of genetically characterized rhesus macaques of Indian-ancestry that are specific pathogen-free (SPF) for an expanded list of 7 persistent viruses, including simian immunodeficiency virus (SIV), simian type D retrovirus (SRV), simian T-lymphotropic virus (STLV), Cercopithecine herpesvirus 1 (B virus), simian foamy virus (SFV), rhesus cytomegalovirus (RhCMV) and rhesus rhadinovirus (RRV). This proposed expansion will be geared to the production of SPF animals for use in AIDS-related research, and to establishing a long-term SPF breeding colony of Indian-origin rhesus macaques with known pedigrees and well-defined MHC genotypes. To meet these objectives, we will derive SPF offspring from conventional, non-SPF Indian rhesus breeding stock through nursery-rearing of neonates. In addition, we will expand the existing Indian-origin colony that is SPF for 5 persistent viruses (SIV, SRV, STLV, SFV, B virus) through natural breeding and mother-rearing in social groups. An expanded program of MHC typing that includes additional microsatellite loci, class I alleles, and class II genes will be used to characterize offspring and their parents. This expanded MHC typing will allow the identification and definition of immune response genotypes, and will allow for selected breeding to produce animals with specific genetic profiles. We also propose to collect longitudinal data on age-related changes in the major lymphocyte subsets in cohorts of nursery-reared and mother-reared SPF rhesus macaques. Age-specific reference ranges, developed from normal, healthy SPF-rhesus macaques, are essential to more fully understand and utilize the macaque model system, and to provide comparative data allowing for more accurate interpretation of lymphocyte subset phenotype alterations observed in AIDS and other infectious and immunologic diseases. The rhesus monkeys produced as part of this grant will provide valuable resources for AIDS-related research. These animals will be used for research related to vaccine development and anti-viral therapy.