Abstract
We have found a new allele at the structural locus for glucosephosphate isomerase (called Gpi-1 c) in a population of wild mice. The Gpi-1 c allele codes for an enzyme of greater cathodal electrophoretic mobility than either the Gpi-1 a or Gpi-1 b alleles found in the wild and in the SM/J and C57BL/6J inbred strains. Mice homozygous for Gpi-1 c have erythrocyte enzyme activity reduced to 33% of normal levels, altered pH profile, lowered heat stability, and normal K m 's when compared with SM/J and C57BL/6J mice. The activity of the enzyme in brain, liver, and kidney is not so markedly lowered, although the electrophoretic mobility, pH profile, and heat stability are altered in these tissues. Deficiencies of erythrocyte glucosephosphate isomerase in man, to this level, can cause severe hemolytic anemia. Homozygotes for Gpi-1 c show only mild hematological symptoms. The frequency of Gpi-1 c in wild populations of mice is discussed and the occurrence of a further rare allele Gpi-1 d is reported.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Arnold, H., Blume, K.-G., Engelhardt, R., and Löhr, G. W. (1973). Glucose isomerase deficiency: Evidence for in vitro instability of an enzyme variant with hemolysis Blood 41691.
Arnold, H., Blume, K.-G., Löhr, G. W., Schroter, W., Koch, H. H., and Wonneberger, B. (1974). Glucose phosphate isomerase deficiency with congenital nonspherocytic hemolytic anaemia: a new variant (type Nordhorn). II. Purification and biochemical properties of the defective enzyme. Pediat. Res. 818.
Baughan, M. A., Valentine, W. N., Paglia, D. E., Ways, P. O., Simons, E. R., and DeMarsh, Q. B. (1968). Hereditary hemolytic anaemia associated with glucosephosphate isomerase (GPI) deficiency—A new enzyme defect of human erythrocytes. Blood 32236.
Berry, R. J., and Peters, J. (1977). Heterogenous heterozygosities in Mus musculus populations. Proc. Roy. Soc. London Ser. B 197485.
Blake, R. L., and Russell, E. S. (1972). Hyperprolinemia and prolinuria in a new inbred strain of mice, PRO/Re. Science 176809.
Blume, K.-G., Hryniuk, W., Powars, D., Trinidad, F., West, C., and Beutler, E. (1972). Characterisation of two new variants of glucose-phosphate-isomerase deficiency with hereditary nonspherocytic hemolytic anemia. J. Lab. Clin. Med. 79942.
Bulfield, G. (1972). Genetic control of metabolism: Enzyme studies of the obese and adipose mutants in the mouse. Genet. Res. 2051.
Bulfield, G. (1977). Nutrition and animal models of inherited metabolic disease. Proc. Nutr. Soc. 3661.
Bulfield, G., and Kacser, H. (1974). Histidinemia in mouse and man. Arch. Dis. Childh. 49545.
Bulfield, G., and Moore, E. A. (1974). Semi-automated assays for enzymopathies of carbohydrate metabolism in liver and erythrocytes using a reaction rate analyser. Clin. Chim. Acta 53265.
Bulfield, G., Moore, E. A., and Kacser, H. (1977). Genetic variation in activity of the enzymes of glycolysis and gluconeogenesis between inbred strains of mice. Submitted for publication.
Carter, N. D., and Parr, C. W. (1967). Isoenzymes of phosphoglucose isomerase in mice. Nature 216511.
DeLorenzo, R. J., and Ruddle, F. H. (1969). Genetic control of two electrophoretic variants of glucosephosphate isomerase in the mouse (Mus musculus). Biochem. Genet. 3151.
Gross, S. R., Longshore, M. A., and Pengburn, S. (1975). The phosphorylase kinase deficiency (Phk) locus in the mouse: Evidence that the mutant allele codes for an enzyme with an abnormal structure. Biochem. Genet. 13567.
Hutton, J. J., and Chilcote, R. R. (1974). Glucose phosphate isomerase deficiency with hereditary nonspherocytic hemolytic anemia. J. Pediat. 85494.
Kacser, H., and Burns, J. A. (1968). Causality, complexity and computers. In Locker, A. (ed.), Quantitative Biology of Metabolism, Third International Symposium Biologische Anstalt Helgoland, Springer-Verlag, Berlin, pp. 11–23.
Kacser, H., and Burns, J. A. (1973). The control of flux. In Davies, D. D. (ed.), Rate Control of Biological Processes, Symp. Soc. Exp. Biol. No. 27, Cambridge University Press, Cambridge, pp. 65–104.
Kacser, H., Bulfield, G., and Wallace, M. E. (1973). Histidinaemic mutant in the mouse. Nature 24477.
Kahn, A., Vives, J.-L., Bertrand, O., Cottreau, D., Mairie, J., and Boivin, P. (1976). Glucose-phosphate isomerase deficiency due to a new variant (GPI Barcelona) and to a silent gene: Biological, immunological and genetic studies. Clin. Chim. Acta 66145.
Löhr, H. W., Arnold, H., and Blume, K.-G. (1973). Hereditary deficiency of glucosephosphate isomerase as a cause of nonspherocytic hemolytic anaemia. Blut 26393.
McKusick, V. A. (1975). Mendelian Inheritance in Man, 4th ed., Johns Hopkins Press, Baltimore.
Nakashima, K., Miwa, S., Oda, S., Oda, E., Matsumoto, N., Fukumoto, Y., and Yamada, T. (1973). Electrophoretic and kinetic studies of glucosephosphate isomerase (GPI) in two different Japanese families with GPI deficiency. Am. J. Hum. Genet. 25294.
Paglia, D. E., and Valentine, W. N. (1974). Hereditary glucosephosphate isomerase deficiency: A review. Am. J. Clin. Pathol. 62740.
Paglia, D. E., Holland, P., Baugham, M. A., and Valentine, W. N. (1969). Occurrence of defective hexosephosphate isomerization in human erythrocytes and leukocytes. New Engl. J. Med. 28066.
Paigen, K. (1971). Genetics of enzyme realization. In Rechigl, M. (ed.) Enzyme Synthesis and Degradation in Mammalian Systems, Karger, Basel, pp. 1–46.
Paigen, K., Swank, R. T., Tomino, S., and Ganschow, R. E. (1975). The molecular genetics of mammalian glucuronidase. J. Cell. Physiol. 85379.
Roderick, T. H., Ruddle, F. H., Chapman, V. M., and Shows, T. B. (1971). Biochemical polymorphisms in feral and inbred mice (Mus musculus). Biochem. Genet. 5457.
Selwyn, J. G., and Dacie, J. V. (1954). Autohemolysis and other changes resulting from the incubation in vitro of red cells from patients with congenital hemolytic anaemia. Blood 9414.
Shows, T. B., and Ruddle, F. H. (1968). Malate dehydrogenase: Evidence for tetrameric structure in Mus musculus. Science 1601356.
Swick, R. W. (1958). Measurement of protein turnover in rat liver. J. Biol. Chem. 231751.
Van Biervliet, J. P. G. M., Van Milligen-Boersma, L., and Staal, G. E. J. (1975a). A new variant of glucosephosphate isomerase deficiency (GPI-Utrecht). Clin. Chim. Acta 65157.
Van Biervliet, J. P. G. M., Vlug, A., Bartstra, H., Rottereel, J. J., de Vaan, G. A. M., and Staal, G. E. J. (1975b). A new variant of glucosephosphate isomerase deficiency. Humangenetik 3035.
Vives-Corrons, J. L., Rozman, C., Kahn, A., Carrera, A., and Triginer, J. (1975). Glucosephosphate isomerase deficiency with hereditary hemolytic anaemia in a Spanish family: Clinical and familial studies. Humangenetik 29291.
Yoshida, A., Beutler, E., and Motulsky, A.-G. (1971). Human glucose-6-phosphate dehydrogenase variants. Bull. WHO 45243.
Author information
Authors and Affiliations
Additional information
This work was supported by M.R.C. grants to Professor R. J. Berry and Dr. H. Kacser, whom we should also like to thank for much help and useful discussion.
Rights and permissions
About this article
Cite this article
Padua, R.A., Bulfield, G. & Peters, J. Biochemical genetics of a new glucosephosphate isomerase allele (Gpi-1 c) from wild mice. Biochem Genet 16, 127–143 (1978). https://doi.org/10.1007/BF00484389
Received:
Revised:
Issue Date:
DOI: https://doi.org/10.1007/BF00484389