NONHUMAN PRIMATE MODEL FOR KRABBE'S DISEASE

这个子项目是许多利用 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 这项提案的长期目标是扩大和研究我们的群体的非人灵长类动物受影响的球状细胞脑白质营养不良（GLD;克拉伯病）。这个猕猴群体代表了世界上唯一一个非人灵长类群体，其中遗传性溶酶体疾病已被确认，繁殖，并可用于研究。 这项R24补助金的主要重点是通过严格的自然繁殖计划显着提高生产受GLD影响的猕猴的效率。 有13个已建立的后宫繁殖组，包括一个携带者男性和携带者和正常女性的组合。这些社会群体是根据携带者群体的谱系数据以及可以与携带者男性一起放置的正常女性的可用性创建的。 绒毛取样进行产前诊断。 在21例已知妊娠中，有19例活产（2例受影响，7例携带者，10例正常）和2例胎儿死亡（遗传状态未知）。我们继续描述疾病的发病机制，并通过分子、生化、临床、行为和病理分析生成受影响动物的数据库，以在非人灵长类动物模型中建立广泛的疾病进展知识基线。 2007年存活的受影响婴儿的特征一直持续到2008年，直到其在276日龄时死亡。 2008年受影响的一名婴儿在74天大时死亡，另一名婴儿在227天大时死亡，数据仍在继续收集。 作为整个动物研究的有效替代方案，我们已经启动了GLD动物的细胞和组织库计划。该计划的主要目标是为研究人员提供活细胞（外周血和骨髓单核细胞，间充质干细胞和皮肤成纤维细胞）和组织样本（主要器官系统）。 截至2008年12月，有42只杂合（携带者）动物：27只繁殖年龄动物（13只雄性和14只雌性），6只幼仔（5只雄性和1只雌性）和9只幼仔/一岁幼仔（5只雄性，4只雌性）。

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. The long-term goal of this proposal is to expand and study our colony of nonhuman primates affected with Globoid Cell Leukodystrophy (GLD; Krabbe's disease). This colony of rhesus monkeys represents the only colony of nonhuman primates in the world in which an inherited lysosomal disorder has been recognized, propagated, and is available for study. The primary focus of this R24 grant is to markedly improving the efficiency of producing macaques affected with GLD through a stringent natural breeding program. There are 13 established harem breeding groups containing a carrier male and a combination of carrier and normal females. These social groups have been created based on pedigree data from the carrier colony as well as the availability of normal females who could be placed with carrier males. Chorionic villi sampling was performed for prenatal diagnosis. Of the 21 known pregnancies, there were 19 live births (2 affected, 7 carrier, 10 normal) and 2 fetal deaths (genetic status unknown). We continue to characterize disease pathogenesis and generate a database with the affected animals through molecular, biochemical, clinical, behavioral, and pathologic analyses to develop an extensive baseline of knowledge of disease progression in the nonhuman primate model. The surviving 2007 affected infant was characterized through 2008 until its death at 276 days of age. One of the 2008 affected infants died at 74 days of age while the other infant is 227 days old and data continues to be collected. As an effective alternative to whole animal studies, we have initiated a cell and tissue banking program for the GLD animals. The primary goal for this program is to make viable cells (peripheral blood and bone marrow mononuclear cells, mesenchymal stem cells, and skin fibroblasts) and tissue samples (primary organ systems) available to investigators for their research. As of December 2008, there are 42 heterozygous (carrier) animals: 27 breeding age animals (13 males and 14 females), 6 juveniles (5 males and 1 female), and 9 infants/yearlings (5 males, 4 females).