Glb1, encoding lysosomal β -galactosidase, is crucial in lysosomal function. Mutations in Glb1 lead to GM1 gangliosidosis, a lysosomal storage disorder. The gene is also associated with cellular senescence, as senescence-associated β -galactosidase (SA-β -gal) activity is expressed from GLB1 [3]. Mouse models are valuable for studying Glb1 function.

A Glb1 knockout mouse model generated using Nuclease technology genome editing mimics the natural history of type II GM1 gangliosidosis patients. The Glb1-/-mice have small deletions in exons 2 and 6, resulting in a null allele. They show progressive motor abnormalities, cerebellar atrophy, accumulation of glycosphingolipids in the brain, and increased levels of a novel pentasaccharide biomarker in urine and plasma, similar to what is observed in patients [2]. Another study generated a Glb1 + / m-Glb1-2A-mCherry (GAC) reporter allele at the Glb1 gene locus. The GAC signal linearly correlates with chronological age in middle-aged mice, is associated with cardiac hypertrophy and a shortened lifespan, and can monitor systemic aging and function decline [1].

In conclusion, Glb1 is essential for normal lysosomal function and its deficiency leads to GM1 gangliosidosis. Glb1-related mouse models, such as the knockout and reporter models, have provided valuable insights into the disease mechanisms and the role of Glb1 in aging-related processes. These models are important for understanding the biological functions of Glb1 and developing new therapies for GM1 gangliosidosis and potentially other age-related conditions.