GAUCHER DISEASE STUDY

这个子项目是许多研究子项目中的一个 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。 拟议研究的总体目标是阐明导致戈谢病（一种典型的先天性代谢缺陷）显著表型变异的分子机制。 戈谢病是由于缺乏酸性β-葡糖苷酶，一种由GBA基因座编码的溶酶体酶。 在这些研究中要解决的两个假设包括：1）GBA基因座的多态性变异与已知的疾病相关突变相结合，导致GC的表型变异性和该基因座突变酶的表达改变。 2)以GD为原型的先天性代谢缺陷中酶的体内活性水平是其区域、组织或细胞病理生理学的主要决定因素。

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.