Generalized glycogen storage and cardiomegaly in a knockout mouse model of Pompe disease

Glycogen storage disease type II (GSDII; Pompe disease), caused byinherited deficiency of acid alpha-glucosidase, is a lysosomal disorderaffecting heart and skeletal muscles. A mouse model of this disease wasobtained by targeted disruption of the murine acid alpha-glucosidase gene(Gaa) in embryonic stem cells. Homozygous knockout mice (Gaa -/-) lack GaamRNA and have a virtually complete acid alpha-glucosidase deficiency.Glycogen-containing lysosomes are detected soon after birth in liver, heartand skeletal muscle cells. By 13 weeks of age, large focal deposits ofglycogen have formed. Vacuolar spaces stain positive for acid phosphataseas a sign of lysosomal pathology. Both male and female knockout mice arefertile and can be intercrossed to produce progeny. The first born knockoutmice are at present 9 months old. Overt clinical symptoms are still absent,but the heart is typically enlarged and the electrocardiogram is abnormal.The mouse model will help greatly to understand the pathogenic mechanism ofGSDII and is a valuable instrument to explore the efficacy of differenttherapeutic interventions.