Proefschrift
Macrophage cell models for the investigation of Gaucher disease
Gaucher disease is a rare metabolic disorder, in which a mutation of the enzyme glucocerebrosidase (GBA1) causes buildup of its substrate glucosylceramide and the deacylated counterpart glucosylsphingosine in lysosomes.
- Auteur
- G.A.M. Louwerse
- Datum
- 06 januari 2026
- Links
- Thesis in Leiden Repository
This buildup is particularly present in macrophages residing in the liver and spleen. Currently, it is difficult to make an accurate genotype-phenotype correlation for this disease. In order to rectify this situation, an accurate, reliable and readily available model of this disease must be established. In this thesis, different macrophage cell lines and primary macrophages were investigated in their potential use as a model for Gaucher disease. GBA1 deficiency was induced by chemical inactivation of GBA1 using specific small molecule inhibitors. While all macrophages showed accumulation of glucosylceramide, the primary macrophages isolated from blood resembled best the macrophages as found in Gaucher disease patients. These primary macrophages were subsequently investigated on the appearance of their lysosomes both in a Gaucher disease state as well as in an endogenous state. Further research with Gaucher disease models originating from primary macrophages should shed light on the underlying molecular disease mechanisms in Gaucher disease.