Mutations in the lysosomal acid beta-galactosidase (EC 3.2.1.23) underlie two 
different disorders: GM1 gangliosidosis, which involves the nervous system and 
visceral organs to varying extents, and Morquio's syndrome type B (Morquio B 
disease), which is a skeletal-connective tissue disease without any CNS 
symptoms. This article shows that transduction of human GM1 gangliosidosis 
fibroblasts with retrovirus vectors encoding the human acid beta-galactosidase 
cDNA leads to complete correction of the enzymatic deficiency. The newly 
synthesized enzyme is correctly processed and targeted to the lysosomes in 
transduced cells. Cross-correction experiments using retrovirus-modified cells 
as enzyme donors showed, however, that the human enzyme is transferred at low 
efficiencies. Experiments using a different retrovirus vector carrying the human 
cDNA confirmed this observation. Transduction of human GM1 fibroblasts and mouse 
NIH 3T3 cells with a retrovirus vector encoding the mouse beta-galactosidase 
cDNA resulted in high levels of enzymatic activity. Furthermore, the mouse 
enzyme was found to be transferred to human cells at high efficiency. Enzyme 
activity measurements in medium conditioned by genetically modified cells 
suggest that the human beta-galactosidase enzyme is less efficiently released to 
the extracellular space than its mouse counterpart. This study suggests that 
lysosomal enzymes, contrary to the generalized perception in the field of gene 
therapy, may differ significantly in their properties and provides insights for 
design of future gene therapy interventions in acid beta-galactosidase 
deficiency.