Genetic complementation in somatic cell hybrids of four variants of infantile GM2 gangliosidosis.
Cell hybridizations between fibroblasts of four variants (B, O, AB, and B1) of infantile GM2 gangliosidosis were performed. Cocultivated as well as hybrid cells were analyzed for their capability to degrade exogenously added [3H]-GM2. Hybridization of variant AB fibroblasts with fibroblasts of variant O, variant B, or variant B1 resulted in an enhanced rate of GM2 hydrolysis, showing intergenic complementation. Similar restoration of GM2 catabolism was observed after hybridization of variant B1 cells with variant O, but not with variant B cells. These results indicate that B1 cells carry a mutation in the gene locus for the alpha-subunit of beta-hexosaminidase. Studies of the processing of immature enzyme in variant B1 cells showed the presence of alpha-precursors and mature alpha-chains, but at a lower level as compared to normal cells.
Sonderfeld
S
S
Brendler
S
S
Sandhoff
K
K
Galjaard
H
H
Hoogeveen
A T
AT
D004591:Electrophoresis, Polyacrylamide Gel; D005347:Fibroblasts / Q000201:enzymology / Q000378:metabolism; D005678:G(M2) Ganglioside / Q000235:genetics / Q000378:metabolism; D005733:Gangliosidoses / Q000201:enzymology / Q000235:genetics*; D005816:Genetic Complementation Test; D006596:Hexosaminidases / Q000172:deficiency / Q000235:genetics; D006801:Humans; D006822:Hybrid Cells; D006868:Hydrolysis; D007223:Infant; D013661:Tay-Sachs Disease / Q000201:enzymology / Q000235:genetics; D001619:beta-N-Acetylhexosaminidases
D005678:G(M2) Ganglioside; D006596:Hexosaminidases; D001619:beta-N-Acetylhexosaminidases