GAUCHER DISEASE STUDY

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。 这项拟议研究的总体目标是阐明导致高谢病显著表型变异的分子机制，高谢病是一种典型的先天代谢错误。高谢病是由于缺乏酸性β-葡萄糖苷酶，这是一种由GBA基因编码的溶酶体酶。这些研究中要解决的两个假设包括：1)GBA基因座的多态变异与已知的疾病相关突变一起导致GC的表型变异，并改变该基因座突变酶的表达。2)以GD为原型的先天性代谢障碍患者体内酶的活性水平是其局部、组织或细胞病理生理的主要决定因素。

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 overall objective of the proposed research is to elucidate the molecular mechanisms leading to the remarkable phenotypic variability in Gaucher Disease, a prototype inborn error of metabolism. Gaucher disease is due to the deficiency of acid beta-glucosidase, a lysosomal enzyme encoded by the GBA locus. Two hypotheses to be addressed in these investigations include: 1) that polymorphic variations at the GBA locus in conjunction with known disease-related mutations lead to phenotypic variability of GC and to altered expression of mutant enzymes from this locus. 2) The in vivo activity levels of enzymes in inborn errors of metabolism, with GD as a prototype, is a primary determinant of their regional, tissue or cellular pathophysiology.