Summary
For three patients with the Lesch-Nyhan syndrome the existence of normal amounts of catalytically inactive hypoxanthine-guanine phosphoribosyltransferase (HGPRT) protein was demonstrated by using antibodies against the normal enzyme subunits. The lack of enzyme activity is reverted in virus transformed cells. Individual revertant cell clones contain different HGPRT enzymes as demonstrated here by isoelectric focusing. The data strongly support the idea of a structural gene mutation as the cause of enzyme deficiency in the Lesch-Nyhan syndrome.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Arnold WJ, Meade JC, Kelley WN (1972) Hypoxanthine-guanine phosphoribosyltransferase. Characteristics of the mutant enzyme in erythrocytes from patients with the Lesch-Nyhan syndrome. J Clin Invest 51:1805–1812
Bonner M, Laskey RA (1974) A film detection method for tritium labeled proteins and nucleic acids in polyacrylamide gels. Eur J Biochem 46:83–88
Davies MR, Dean BM (1971) The heterogeneity of erythrocyte IMP-pyrophosphate phosphoribosyltransferase and purine nucleoside phosphorylase by isoelectric focusing. FEBS Lett 18:283–286
Dean MF, Muir H, Benson PF, Button LR, Boylston A, Mowbray J (1976) Enzyme replacement therapy by fibroblast transplantation in a case of Hunter syndrome. Nature 261:323–324
DerKaloustian VM, Awdeh ZL, Hallal RT, Wakid NW (1973) Analysis of human HGPRT-isozymes by isoelectric focusing in polyacrylamide gel. Biochem Genet 9:91–96
Ghangas GS, Milman G (1975) Radioimmune determination of HGPRT cross-reacting material in erythrocytes of Lesch-Nyhan patients. Proc Natl Acad Sci USA 72:4147–4150
Kelley WN, Meade JC (1971) Studies on HGPRT in fibroblasts from patients with the Lesch-Nyhan syndrome. Evidence for genetic heterogeneity. J Biol Chem 246:2953–2958
Knapp A, Grimm H, Ladstädter L, Schlenzka K, Weber A, Langer P (1977) Lesch-Nyhan Syndrom. Dtsch Gesundh Wesen 32:1681–1686
Lesch M, Nyhan WL (1964) A familian disorder of uric acid metabolism and central nervous system function. Am J Med 36:561–570
Lübbe L, Strauss M, Geissler E (1979) Reversion of HGPRT deficiency of skin fibroblasts from Lesch-Nyhan patients. Proc of the 12th FEBS Meeting Dresden, Vol 56. Pergamon Press, p 67
Lübbe L, Strauss M, Scherneck S, Geissler E (to be published) Reversion of HGPRT-deficiency in skin fibroblasts from Lesch-Nyhan patients as a result of transformation by SV40. Exp Cell Res
Mulligan RC, Howard BH, Berg P (1979) Synthesis of rabbit β-globin in cultured monkey kidney cells following infection with a SV40 β-globin recombinant genome. Nature 277:108–114
Rubin CS, Dancis J, Yip LC, Nowinski RC, Balis ME (1971) Purification of IMP: pyrophosphate phosphoribosyltransferase, catalytically incompetent enzymes in Lesch-Nyhan disease. Proc Natl Acad Sci USA 68:1461–1464
Seegmiller JE, Rosenbloom FM, Kelley WN (1967) enzyme defect associated with a sex-linked human neurological disorder and excessive purine synthesis. Science 155:1682–1684
Strauss M (1975) Determination of the subunit molecular weight of hypoxanthine-guanine phosphoribosyltransferase from human erythrocytes by recovery of enzyme activity from sodium dodecylsulfate gels. Biochim Biophys Acta 410:426–430
Strauss M (1977) Vergleichende Untersuchungen zur Struktur und Funktion von Hypoxanthin-Guanin Phosphoribosyltransferasen. Dr. rer. nat. thesis, Academy of Sciences of the GDR, Berlin
Strauss M, Behlke J, Goerl M (1978a) Evidence against the existence of real isozymes of hypoxathine phosphoribosyltransferase. Eur J Biochem 90:89–97
Strauss M, Theile M, Eckert R, Geissler E (1978b) Detection of antigenetically active mutant HGPRT after mutagenesis with Simian virus 40. Mutat Res 51:297–300
Strauss M, Behlke J, Lübbe L, Theile M, Geissler E (1979) Hypoxanthine-guanine phosphoribosyltransferase from normal, mutant, and revertant cells. 11th International Congress of Biochemistry, 8.–13.July 1979, Toronto, Canada. Book of Abstract, p 648
Theile M, Scherneck S, Geissler E (1976) Mutagenesis by Simian virus 40. I. Detection of Mutations in Chinese hamster cell lines using different resistance markers. Mutat Res 37:111–124
Theile M, Strauss M (1977) Mutagenesis by Simian virus 40. II. Changes in substrate affinities in mutant hypoxanthine-guanine phosphoribosyltransferase enzymes at different pH values. Mutat Res 45: 111–123
Theile M, Strauss M, Lübbe L, Scherneck S, Krause H, Geissler E (1980) SV40-induced somatic mutations: possible relevance to viral transformation. Cold Spring Harbor Symp Quant Biol 44:377–382
Tischfield JA, Bernhard MP, Ruddle FH (1973) A new electrophoreticautoradiographic method for the visual detection of phosphotransferases. Anal Biochem 53:454–554
Upchurch KS, Leyva A, Arnold WJ, Holmes EW, Kelley WN (1975) HGPRT deficiency: association of reduced catalytic activity with reduced levels of immunologically detectable enzyme protein. Proc Natl Acad Sci USA 72:4142–4146
van Diggelen OP, McGarrity GJ, Shin S-I (1978) Endogenous hypoxanthine phosphoribosyltransferase activty in mycoplasmas isolated from cell cultures. In Vitro 14:734–739
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Strauss, M., Lübbe, L. & Geissler, E. HGPRT structural gene mutation in Lesch-Nyhan-syndrome as indicated by antigenic activity and reversion of the enzyme deficiency. Hum Genet 57, 185–188 (1981). https://doi.org/10.1007/BF00282019
Received:
Revised:
Issue Date:
DOI: https://doi.org/10.1007/BF00282019