Gaucher disease (GD), a common lysosomal storage disorder (LSD), is caused by
mutations in the GBA1 gene. This gene encodes the lysosomal hydrolase
glucocerebrosidase (GlcCerase), and in the disease, the lipid glucosylceramide
(GlcCer) accumulates within the cell. Although neuronopathic Gaucher disease (nGD) was described over a hundred years ago, little is known about the mechanisms leading from GlcCer accumulation to neuronal cell death and inflammation. Recently, our laboratory identified induction of the type 1 interferon (IFN) response in nGD mice. The IFN response is the fundamental cellular defense mechanism against viral infection, however it can also be induced in the absence of infection. Ablation of the IFN receptor (IFNAR) did not have any effect on the viability of nGD mice. Therefore, we took availability of quadrat deficient mice where four adaptors of main pathogen recognition receptors (PRR) are blocked. Ablation of all the pathways leading to IFN production did not have effect on mice life span. Nevertheless, we utilized these results to conduct an RNA sequencing study with the goal of defining what are the inflammatory pathways lead to disease development and, eventually, to mice death.
