Correction of I-cell defect by hybridization with lysosomal enzyme deficient human fibroblasts

I-cell fibroblasts with a multiple intracellular lysosomal enzyme deficiency were hybridized with cells from patients with different types of single lysosomal enzyme defects. Fusion with G_M2 gangliosidosis, type 2, (Sandhoff disease) fibroblasts resulted in a restoration of the hexosaminidase activity, in a normalization of the electrophoretic mobility of the isoenzymes, and in a decreased activity in the medium. Fusion of I-cells with fibroblasts from G_M1 gangliosidosis, type 1, led to enhancement of β-galactosidase (β-gal) activity. This complementation must be the result of the presence of normal polypeptide chains in I-cells, whereas the other cell types provide a factor that causes the intracellular retention of the enzymes. Restoration of β-gal was also observed in heterokaryons after fusion of I-cells with β-galactosidase/neuraminidase-deficient (β-gal⁻/neur⁻) variants, indicating that the neuraminidase(s) and the posttranslational modification of β-gal are affected in a different way in I-cell disease and in β-gal⁻/neur⁻ variants. Fusion of I-cells with mannosidosis fibroblasts resulted in a restoration of the acidic form of α-mannosidase and in a decrease of the extracellular activity of both this enzyme and the hexosaminidase enzyme, indicating that fusion of I-cells with different types of fibroblasts with a single lysosomal enzyme deficiency not only leads to complementation for one particular enzyme but also to a correction of the basic defect in I-cells.