Hypoxanthine-Guanine Phosphoribosyltransferase Deficiency: Chemical Agents Selective for Mutant or Normal Cultured Fibroblasts in Mixed and Heterozygote Cultures

Cultured fibroblasts established from skin biopsies from patients with the Lesch-Nyhan syndrome are deficient in hypoxanthine-guanine phosphoribosyltransferase (EC 2.4.2.8) activity. This deficiency makes possible the use of chemicals that select either for or against deficient variants in cultured...

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Bibliographic Details
Published in:Proceedings of the National Academy of Sciences - PNAS 1971-07, Vol.68 (7), p.1516-1519
Main Authors: Fujimoto, Wilfred Y., Subak-Sharpe, John H., Seegmiller, J. Edwin
Format: Article
Language:English
Subjects:
Autoradiography
Azaserine - pharmacology
Biological Sciences: Genetics
Cell Line - drug effects
Cell Line - enzymology
Cell lines
Culture Techniques
Cultured cells
Fibroblasts
Fibroblasts - drug effects
Fibroblasts - enzymology
Flasks
Genetics, Medical
Guanine Nucleotides
Heterozygote
Heterozygotes
Humans
Hypoxanthines - metabolism
Hypoxia
Lesch-Nyhan Syndrome
Mutation
Nucleic acids
Nucleotides
Pentosephosphates
Purines
Selection, Genetic
Skin
Somatic cells
Thioguanine - pharmacology
Time Factors
Transferases - analysis
Tritium
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Summary:Cultured fibroblasts established from skin biopsies from patients with the Lesch-Nyhan syndrome are deficient in hypoxanthine-guanine phosphoribosyltransferase (EC 2.4.2.8) activity. This deficiency makes possible the use of chemicals that select either for or against deficient variants in cultured fibroblasts. Two-way selection has been achieved by the use of 6-thioguanine, which selects for the deficient mutant, and azaserine, which selects to some extent for the normal allele in mixed cultures, as well as in cultures from heterozygotes. Theoretical considerations predict that the phenomenon of metabolic cooperation would tend to reinforce the former and to weaken the latter type of selection, and this is in accordance with the experimental findings.
ISSN:0027-8424
1091-6490
DOI:10.1073/pnas.68.7.1516