Disease relevance of Gaa

• We have made transgenic lines expressing human GAA in skeletal and cardiac muscle of Gaa(-/-) mice, and we turned the transgene on at different stages of disease progression by using a tetracycline-controllable system [1].
• We have assessed the utility of recombinant adeno-associated virus (rAAV) vectors to restore GAA activity in vivo in a mouse model of GSDII (Gaa(-/-)) [2].
• Pompe disease (glycogen storage disease type II) is a glycogen storage disease caused by a deficiency of the lysosomal enzyme, acid maltase/acid alpha-1,4 glucosidase (GAA) [3].

High impact information on Gaa

• A mouse model of this disease was obtained by targeted disruption of the murine acid alpha-glucosidase gene (Gaa) in embryonic stem cells [4].
• Furthermore, functional correction of the soleus skeletal muscle was also observed compared to age-matched untreated Gaa(-/-) control animals [2].
• However, in skeletal muscle-a major organ affected in infantile and in milder, late-onset variants in humans-induction of GAA expression in young Gaa(-/-) mice to levels greatly exceeding wildtype values did not result in full phenotypic correction, and some muscle fibers showed little or no glycogen clearance [1].
• Mice defective in the GAA gene encoding lysosomal alpha-glucosidase (acid maltase) overaccumulate glycogen in the lysosome but did not have elevated laforin [5].
• Inheritance in recombinant inbred (RI) strains of restriction fragment length variants (RFLVs) detected by probes specific for Gaa and Tk-1 showed tight linkage of both to Es-3 on mouse Chromosome (Chr) 11 [6].

Associations of Gaa with chemical compounds

• In freely fed mice the glycogen-hydrolysing activity (acid amyloglucosidase) was only 50% of the maltose-hydrolysing activity (acid maltase) [7].

References