NONHUMAN PRIMATE MODEL FOR KRABBE'S DISEASE

点击翻译按钮获取中文摘要

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).