NONHUMAN PRIMATE MODEL FOR KRABBE'S DISEASE

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。 这项提议的长期目标是扩大和研究我们的非人类灵长类动物群体，这些灵长类动物患有球状细胞白血病营养不良症(GLD；Krabbe病)。这群恒河猴代表了世界上唯一一群非人类灵长类动物，在其中遗传性溶酶体疾病已被识别、繁殖并可用于研究。这笔R24赠款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。已建立的后宫繁育群有13个，包括一个携带者雄性和一个携带者和正常雌性的组合。这些社会群体是基于携带者群体的血统数据以及可以与携带者男性配对的正常雌性的可用性而创建的。取绒毛标本进行产前诊断。在已知的21例妊娠中，有19例活产(2例感染，7例携带者，10例正常)，2例胎儿死亡(遗传状况不明)。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，与受影响的动物建立数据库，以建立非人类灵长类动物模型中疾病进展的广泛基线知识。幸存的2007年受影响婴儿的特征是从2008年一直到276天大时死亡。2008年受影响的婴儿中，一名在74天大时死亡，另一名婴儿在227天大，正在继续收集数据。作为整个动物研究的有效替代方案，我们为GLD动物启动了一个细胞和组织库计划。该计划的主要目标是使活细胞(外周血和骨髓单个核细胞、间充质干细胞和皮肤成纤维细胞)和组织样本(初级器官系统)可供研究人员使用。截至2008年12月，有42只杂合子(携带者)动物：27只处于繁殖年龄的动物(13只雄性和14只雌性)，6只青少年(5只雄性和1只雌性)，以及9只婴儿/一岁幼崽(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).