Acid alpha-glucosidase (GAA) deficiency causes Pompe disease, a lethal lysosomal 
glycogen storage disease for which no effective treatment currently exists. We 
investigated the endocytic process in deficient cells of human recombinant GAA 
produced in Chinese hamster ovary cells, and the potential of GAA-deficient 
Japanese acid maltase-deficient quail as a model for evaluating the enzyme 
replacement therapy for Pompe disease. After 24-h incubation with a single dose 
of recombinant enzyme, intracellular GAA and glycogen levels in deficient human 
fibroblasts were normalized, and this correction lasted for 7 d. The 110-kD 
precursor recombinant enzyme was processed to the 76-kD mature form within 24 h 
after uptake. Intracellular GAA levels in deficient quail fibroblasts and 
myoblasts were similarly corrected to their average normal levels within 24 h. 
Differences existed in the efficiency of endocytosis among subfractions of the 
enzyme, and among different cell types. Fractions with a larger proportion of 
precursor GAA were endocytosed more efficiently. Quail fibroblasts required a 
higher dose, 4200 nmol.h-1.mL-1 to normalize intracellular GAA levels than human 
fibroblasts, 1290 nmol.h-1.mL-1, whereas primary quail myoblasts required 2800 
nmol.h-1.mL-1. In all three cell lines, the endocytosed enzyme localized to the 
lysosomes on immunofluorescence staining, and the endocytosis was inhibited by 
mannose 6-phosphate (Man-6-P) added to the culture medium. Despite structural 
differences in Man-6-P receptors between birds and mammals, these studies 
illustrate that Man-6-P receptor mediated endocytosis is present in quail muscle 
cells, and demonstrate the potential of acid maltase-deficient quail to test 
receptor mediated enzyme replacement therapy for Pompe disease.