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 beta-galactosidase (beta-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 beta-gal was also observed in heterokaryons after fusion of I-cells with beta-galactosidase/neuraminidase-deficient (beta-gal(-)/neur(-)) variants, indicating that the neuraminidase(s) and the posttranslational modification of beta-gal are affected in a different way in I-cell disease and in beta-gal(-)/neur(-) variants. Fusion of I-cells with mannosidosis fibroblasts resulted in a restoration of the acidic form of alpha-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.
D002459:Cell Fusion; D002478:Cells, Cultured; D005347:Fibroblasts / Q000201:enzymology*; D005733:Gangliosidoses / Q000201:enzymology; D005816:Genetic Complementation Test; D006596:Hexosaminidases / Q000378:metabolism; D006801:Humans; D006822:Hybrid Cells / Q000201:enzymology*; D008247:Lysosomes / Q000201:enzymology; D008361:Mannosidases / Q000378:metabolism; D009081:Mucolipidoses / Q000201:enzymology*; D012497:Sandhoff Disease / Q000201:enzymology; D001616:beta-Galactosidase / Q000378:metabolism
D006596:Hexosaminidases; D008361:Mannosidases; D001616:beta-Galactosidase