Proceedings of the National Academy of Sciences, 1975
Diphtheria toxin inhibits protein synthesis in eukaryotic cells by catalyzing inactivation of elo... more Diphtheria toxin inhibits protein synthesis in eukaryotic cells by catalyzing inactivation of elongation factor 2. The 10,000-fold greater sensitivity in vitro to diphtheria toxin of human cells as compared to mouse cells seems to be attributable to a difference at the level of the cell membrane. Mouse-human cell hybrids are as sensitive to diphtheria toxin as human cells. We have shown that the sensitivity of the hybrid cells is due to a gene or genes located on human chromosome 5. Mouse-human hybrid cells in which chromosome 5 is present are as sensitive to the toxin as human cells, which hybrids without chromosome 5 are as resistant as mouse cells. Entry of toxin into cells seems to be a two-step process involvin, (1) binding of toxin to the cell surface and (2) endocytotic uptake of toxin. The difference in sensitivity between human and mouse cells and between hybrid cells with and without chromosome 5 does not appear to be due to a difference in endocytotic activity and may be ...
Proceedings of the National Academy of Sciences, 1974
A total of 40 mouse-human cell hybrids were induced with poly(I)·poly(C) and with Newcastle disea... more A total of 40 mouse-human cell hybrids were induced with poly(I)·poly(C) and with Newcastle disease virus. Ten hybrid clones produced low levels of human interferon in response to both the virus and poly(I)·poly(C). Concurrent enzymic and chromosomal analysis of the hybrid clones indicated a concordant segregation of these levels of human interferon with chromosomes 2 and 5. The presence of both chromosomes 2 and 5 was necessary for interferon production; neither was sufficient alone. Based on this finding, we postulate that there are at least two asyntenic gene loci for the expression of interferon in human cells.
Proceedings of the National Academy of Sciences, 1975
The techniques of somatic cell genetics have been used to establish the linkage relationships of ... more The techniques of somatic cell genetics have been used to establish the linkage relationships of loci coding for two forms (A and B) of hexosaminidase (EC 3.2.1.30; 2-acetamido-2-deoxy-beta-D-glucoside acetamidodeoxyglucohydrolase) and to determine whether a structural relationship exists between these forms. In a series of human-mouse hybrid cell lines, hexosaminidase A and B segregated independently. Our results and those reported by other investigators are used to analyze the proposed structural models for hexosaminidase. We have also been able to establish a syntenic relationship between the gene locus responsible for the expression of hexosaminidase A and those responsible for mannosephosphate isomerase and pyruvate kinase-3 and to assign the gene for hexosaminidase B to chromosome 5 in man. There is thus a linkage between specific human autosomes and enzymes implicated in the production of lipid storage diseases.
Evidence based on analysis of mouse-human somatic-cell hybrids is presented that supports the ass... more Evidence based on analysis of mouse-human somatic-cell hybrids is presented that supports the assignment for the structural loci of peptidase A to human chromosome 18 and of cytoplasmic glutamate oxaloacetate transaminase (GOT) (EC 2.6.1.1) to chromosome 10. The medical and evolutionary significance of these assignments is discussed.
Proceedings of the National Academy of Sciences, 1975
Diphtheria toxin inhibits protein synthesis in eukaryotic cells by catalyzing inactivation of elo... more Diphtheria toxin inhibits protein synthesis in eukaryotic cells by catalyzing inactivation of elongation factor 2. The 10,000-fold greater sensitivity in vitro to diphtheria toxin of human cells as compared to mouse cells seems to be attributable to a difference at the level of the cell membrane. Mouse-human cell hybrids are as sensitive to diphtheria toxin as human cells. We have shown that the sensitivity of the hybrid cells is due to a gene or genes located on human chromosome 5. Mouse-human hybrid cells in which chromosome 5 is present are as sensitive to the toxin as human cells, which hybrids without chromosome 5 are as resistant as mouse cells. Entry of toxin into cells seems to be a two-step process involvin, (1) binding of toxin to the cell surface and (2) endocytotic uptake of toxin. The difference in sensitivity between human and mouse cells and between hybrid cells with and without chromosome 5 does not appear to be due to a difference in endocytotic activity and may be ...
Proceedings of the National Academy of Sciences, 1974
A total of 40 mouse-human cell hybrids were induced with poly(I)·poly(C) and with Newcastle disea... more A total of 40 mouse-human cell hybrids were induced with poly(I)·poly(C) and with Newcastle disease virus. Ten hybrid clones produced low levels of human interferon in response to both the virus and poly(I)·poly(C). Concurrent enzymic and chromosomal analysis of the hybrid clones indicated a concordant segregation of these levels of human interferon with chromosomes 2 and 5. The presence of both chromosomes 2 and 5 was necessary for interferon production; neither was sufficient alone. Based on this finding, we postulate that there are at least two asyntenic gene loci for the expression of interferon in human cells.
Proceedings of the National Academy of Sciences, 1975
The techniques of somatic cell genetics have been used to establish the linkage relationships of ... more The techniques of somatic cell genetics have been used to establish the linkage relationships of loci coding for two forms (A and B) of hexosaminidase (EC 3.2.1.30; 2-acetamido-2-deoxy-beta-D-glucoside acetamidodeoxyglucohydrolase) and to determine whether a structural relationship exists between these forms. In a series of human-mouse hybrid cell lines, hexosaminidase A and B segregated independently. Our results and those reported by other investigators are used to analyze the proposed structural models for hexosaminidase. We have also been able to establish a syntenic relationship between the gene locus responsible for the expression of hexosaminidase A and those responsible for mannosephosphate isomerase and pyruvate kinase-3 and to assign the gene for hexosaminidase B to chromosome 5 in man. There is thus a linkage between specific human autosomes and enzymes implicated in the production of lipid storage diseases.
Evidence based on analysis of mouse-human somatic-cell hybrids is presented that supports the ass... more Evidence based on analysis of mouse-human somatic-cell hybrids is presented that supports the assignment for the structural loci of peptidase A to human chromosome 18 and of cytoplasmic glutamate oxaloacetate transaminase (GOT) (EC 2.6.1.1) to chromosome 10. The medical and evolutionary significance of these assignments is discussed.
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