Gba1-flox Mouse

Gba1, which encodes the lysosomal enzyme glucocerebrosidase (GCase), is involved in sphingolipid metabolism [4]. Deficiency in GCase leads to the accumulation of its glycolipid substrates, ultimately resulting in toxicity and inflammation [2]. Mutations in Gba1 are the most common genetic risk factors for Parkinson's disease (PD) and are also associated with Gaucher's disease (GD) [1,3,5].

Mouse models have been used to study Gba1-associated PD. For example, Gba1 E326K knock-in mice show reduced glucocerebrosidase enzymatic activity, glucosylceramide build-up, increased neuroinflammation, and pathogenic α-synuclein transmission, exacerbating disease pathology in PD models [6]. These models help reveal how Gba1 mutations contribute to PD development through mechanisms like lysosomal dysfunction, α-synuclein aggregation, and neuroinflammation [3,5,6].

In conclusion, Gba1 is essential for normal sphingolipid metabolism, and its deficiency has significant implications for PD. Gba1-associated PD mouse models, such as the Gba1 E326K knock-in mice, have enhanced our understanding of the disease mechanisms, providing a basis for developing targeted therapeutic strategies for PD [6].