Glb1, encoding lysosomal β-galactosidase, is of great biological significance. Lysosomal β-galactosidase is involved in the degradation of β-linked galactose-containing glycoconjugates in the lysosomal pathway [2,3]. Mutations in Glb1 are associated with GM1 gangliosidosis, a lysosomal storage disorder [3]. Mouse models are valuable for studying Glb1's functions.

A Glb1 knockout mouse model was generated using Nuclease technology genome editing. Glb1-/-mice have small deletions in exons 2 and 6, creating a null allele. These mice have a lifespan of approximately 50 weeks, with female mice dying six weeks earlier than males. They exhibit progressive gait abnormalities, loss of motor skills, and cerebellar atrophy, similar to type II GM1 gangliosidosis patients. Additionally, Glb1-/-mice show increased levels of a novel pentasaccharide biomarker in urine and plasma, as well as accumulation of glycosphingolipids in the brain [1].

In conclusion, Glb1 is essential for the normal degradation of specific glycoconjugates through its encoded lysosomal β-galactosidase. The Glb1 knockout mouse model closely mimics the features of type II GM1 gangliosidosis, facilitating the understanding of the disease mechanism and guiding the development of new therapies for this disorder [1,3].

References:

1. Nicoli, Elena-Raluca, Huebecker, Mylene, Han, Sangwoo T, Platt, Frances M, Tifft, Cynthia J. 2023. Glb1 knockout mouse model shares natural history with type II GM1 gangliosidosis patients. In Molecular genetics and metabolism, 138, 107508. doi:10.1016/j.ymgme.2023.107508. https://pubmed.ncbi.nlm.nih.gov/36709532/

2. Lee, Bo Yun, Han, Jung A, Im, Jun Sub, DiMaio, Daniel, Hwang, Eun Seong. . Senescence-associated beta-galactosidase is lysosomal beta-galactosidase. In Aging cell, 5, 187-95. doi:. https://pubmed.ncbi.nlm.nih.gov/16626397/

3. Nicoli, Elena-Raluca, Annunziata, Ida, d'Azzo, Alessandra, Tifft, Cynthia J, Stepien, Karolina M. 2021. GM1 Gangliosidosis-A Mini-Review. In Frontiers in genetics, 12, 734878. doi:10.3389/fgene.2021.734878. https://pubmed.ncbi.nlm.nih.gov/34539759/