Genetic complementation in somatic cell hybrids of four variants of infantile GM2 gangliosidosis

Summary Cell hybridizations between fibroblasts of four variants (B, O, AB, and B1) of infantile G_M2 gangliosidosis were performed. Cocultivated as well as hybrid cells were analyzed for their capability to degrade exogenously added ³H]-G_M2. Hybridization of variant AB fibroblasts with fibroblasts of variant O, variant B, or variant B1 resulted in an enhanced rate of G_M2 hydrolysis, showing intergenic complementation. Similar restoration of G_M2 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 α-subunit of β-hexosaminidase. Studies of the processing of immature enzyme in variant B1 cells showed the presence of α-precursors and mature α-chains, but at a lower level as compared to normal cells.