Open AccessHuman β-D- N -Acetylhexosaminidases A and B: Expression and Linkage Relationships in Somatic Cell Hybrids
Author(s) -
Peter A. Lalley,
Mario C. Rattazzi,
Thomas B. Shows
Publication year - 1974
Publication title -
proceedings of the national academy of sciences of the united states of america
Language(s) - English
Resource type - Journals
eISSN - 1091-6490
pISSN - 0027-8424
DOI - 10.1073/pnas.71.4.1569
Subject(s) - biology , sandhoff disease , hexosaminidase , gene , gangliosidosis , genetics , somatic cell , microbiology and biotechnology , enzyme , biochemistry
Knowledge of the genetic relationships between β-D-N -acetylhexosaminidases A and B (EC 3.2.1.30) may help in understanding the hexosaminidase deficiency associated with GM2 gangliosidosis, a fatal lipid storage disease in man. Through the use of man-mouse somatic cell hybrids we have found that a gene involved in hexosaminidase A expression was linked to the genes coding for mannosephosphate isomerase and pyruvate kinase-3. The gene coding for hexosaminidase B was not linked to any of the genes coding for 25 enzyme markers tested. A combination of immunological and electrophoretic techniques was employed to identify human hexosaminidases A and B with certainty in cell hybrids. Discordant segregation of hexosaminidase A and hexosaminidase B in 60 clones indicated that the genes coding for their expression were not linked. However, hexosaminidase A was never expressed in cell hybrids in the absence of hexosaminidase B. This suggests that the gene responsible for the hexosaminidase A phenotype, linked to mannosephosphate isomerase and pyruvate kinase-3, requires the presence of the gene coding for hexosaminidase B for the expression of hexosaminidase A. These observations offer a genetic explanation for the biochemical and immunological relationships between hexosaminidases A and B and provide the framework for identifying the basic genetic defects responsible for GM2 gangliosidosis.