Scientific researchers Cat Lutz and Aamir Zuberi at the Rare Disease Center of the Jackson Laboratory in Bar Harbor, Maine, USA have succeeded in generating two new mouse models for beta-galactosidase deficiency, a rare clinical disorder associated with mutations in the Glb1 b-galactosidase gene.  The two models generated include a mouse strain carrying the murine equivalent of the human leucine to arginine L155R mutation in Glb1.  The mouse L156R mutation is associated with the type 2 (Juvenile) form of the three types of human GM1-deficiency, the others being a type 1 infantile form, typically apparent at 6 months of age, and the type 3 adult-onset form.  There is considerable overlap between the different types of GM1 and it is unclear if background genetic variation can play a role in the age of onset and severity of the disorder.

The presence of a mouse model for type 2 beta-gal deficiency can facilitate research into what other genetic and environmental factors may play a role in influencing the severity of the disease in humans and in understanding the changes in global gene regulation in pre- verses post-symptomatic mutant mice.  The second strain generated at The Jackson Laboratory carries a null mutation in Glb1 resulting in little or no protein being expressed.  Research to analyze the natural history of the disease course in these beta-galactosidase deficient mice is currently underway at The Jackson Laboratory.  These mice will provide a useful tools to the biomedical research community to test the effectiveness of new treatment paradigms, including gene and enzyme replacement therapies to treat and cure beta-galactosidase deficiency.  The mice will also provide a platform for rapidly screening candidate drugs for effectiveness in alleviating the critical symptoms of the disorder.

The natural history studies for these mouse models will help facilitate research and drug development.  Furthermore, at least 3 separate research teams are already planning to utilize these new mouse models.