Mouse Model Created Using Glucocerebrosidase-Deficient Neuronal Cell Line to Study Gaucher Disease Pathophysiology and Evaluate New Therapies

This technology includes a high-yield, easy-to-culture mouse neuronal cell model with nearly complete glucocerebrosidase deficiency representative of Gaucher disease (GD) to study pathophysiology and evaluate new therapies. GD is an autosomal recessive lysosomal storage disorder caused by loss-of function mutations in the GBA1 gene, which codes for the lysosomal hydrolase glucocerebrosidase (GCase). Inventors have successfully immortalized cortical neurons from embryonic null allele GBA-/- mice and the control littermate (GBA+/+) by infecting differentiated primary cortical neurons in culture with an EF1aSV40T lentivirus. Immortalized GBA-/- neurons lack glucocerebrosidase protein and enzyme activity and exhibit a dramatic increase in glucosylceramide and glucosylsphingosine accumulation,enlarged lysosomes, and an impaired ATP-dependent calcium-influx response.