Abstract
A mouse mutant with pyruvate kinase (PK) hyperactivity has been found in offspring of 1-ethyl-1-nitrosourea (ENU)-treated male mice. The activity alteration was detected in the blood and could also be found in the liver but not in the muscle, kidney, heart, spleen, lung, or brain. Heterozygous mice have erythrocyte PK activity enhanced up to about 160% and homozygotes up to about 240%, compared to homozygous wild types. The mutation is codominantly expressed. The heterozygous and homozygous mutants are viable and fully fertile and do not show symptoms of erythrocytosis. The mutation does not affect the heat stability, the electrophoretic mobility, or the K m (for phosphoenolpyruvate) of the PK molecule. It is suggested that the regulatory locus of PK-1 is affected by this mutation. The observations support also the theory of one structural locus for the erythrocyte and liver isozymes.
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References
Anderson, N. G. (1969). A multiple-cuvet rotor for a new microanalytical system. Anal. Biochem. 28545.
Bergmeyer, H. U., Bernt, E., Gawehn, K., and Michal, G. (1974a). Handling of biochemical reagents and samples. In Bergmeyer, H. U. (ed.), Methods of Enzymatic Analysis, Vol. 1 Academic Press, New York, pp. 158–179.
Bergmeyer, H. U., Gawehn, K., and Grassl, M. (1974b). Enzymes as biochemical reagents. In Bergmeyer, H. U. (ed), Methods of Enzymatic Analysis, Vol. 1 Academic Press, New York, pp. 425–522.
Bishop, J. B., and Feuers, R. J. (1982). Development of a new biochemical mutation test in mice based upon measurement of enzyme activities. II. Test results with ethyl methanesulfonate (EMS). Mutat. Res. 95273.
Bulfield, G. (1980). Inherited metabolic disease in laboratory animals: A review. J. Inher. Metab. Dis. 3133.
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., and Moore, K. (1978). Screening and study of inherited enzyme deficiencies of erythrocyte glycolysis and associated pathways in wild mice. Hereditas 89140.
Charles, D. J., and Pretsch, W. (1981). A mutation affecting the lactate dehydrogenase locus Ldh-1 in the mouse. I. Genetical and electrophoretical characterization. Biochem. Genet. 19301.
Charles, D. J., and Pretsch, W. (1982). Activity measurements of erythrocyte enzymes in mice. Detection of a new class of gene mutations. Mutat. Res. 97177.
Charles, D. J., and Pretsch, W. (1983a). Detection of genetic variants by measuring enzyme activities in the blood of mice. Mutat. Res. 113333.
Charles, D. J., and Pretsch, W. (1983b). Detection of mouse mutants with altered enzyme activities. Genet. Res. 41304.
Czok, R., and Lamprecht, W. (1974). Pyruvate, phosphoenolpyruvate and D-glycerate-2-phosphate. In Bergmeyer, H. U. (ed.), Methods of Enzymatic Analysis, Vol. 3 Academic Press, New York, pp. 1446–1451.
Eber, S. W., Dünnwald, M., Belohradsky, B. H., Bidlingmaier, F., Schievelbein, H., Weinmann, H. M., and Krietsch, W. K. (1979). Hereditary deficiency of triosephosphate isomerase in four unrelated families. Eur. J. Clin. Invest. 9195.
Ehling, U. H. (1978). Specific-locus mutations in mice. In Hollaender, A., and de Serres, F. J. (eds.), Chemical Mutagens, Vol. 5 Plenum Press, New York, pp. 233–256.
Ehling, U. H., Favor, J., Kratochvilova, J., and Neuhäuser-Klaus, A. (1982). Dominant cataract mutations and specific-locus mutations in mice induced by radiation or ethylnitrosourea. Mutat. Res. 91181.
Etiemble, J., Picat, C., and Boivin, P. (1982). A red cell pyruvate kinase mutant with normal L-type PK in the liver. Hum. Genet. 61256.
Favor, J. (1983). A comparison of the dominant cataract and recessive specific-locus mutation rates induced by treatment of male mice with ethylnitrosourea. Mutat. Res. 110367.
Feuers, R. J., Bishop, J. B., Delongchamp, R. R., and Casciano, D. A. (1982). Development of a new biochemical mutation test in mice based upon measurement of enzyme activities. I. Theoretical concepts and basic procedure. Mutat. Res. 95263.
Grimes, A. J., Meisler, A., and Dacie, J. V. (1964). Hereditary non-sphaerocytic haemolytic anaemia. A study of red-cell carbohydrate metabolism in twelve cases of pyruvate-kinase deficiency. Br. J. Haematol. 10403.
Johnson, F. M., and Lewis, S. E. (1981). Electrophoretically detected germinal mutations induced in the mouse by ethylnitrosourea. Proc. Natl. Acad. Sci. USA 783138.
Johnson, F. M., Chasalow, F., Anderson, G., MacDougal, P., Hendren, R. W., and Lewis, S. E. (1981). A variation in mouse kidney pyruvate kinase activity determined by a mutant gene on chromosome 9. Genet. Res. 37:123.
Kahn, A., Marie, J., Galand, C., and Boivin, P. (1975). Molecular mechanism of erythrocyte pyruvate kinase deficiency. Humangenetik 29271.
Kahn, A., Marie, J., Galand, C., and Boivin, P. (1976). Chronic haemolytic anaemia in two patients heterozygous for erythrocyte pyruvate kinase deficiency. Electrofocusing and immunological studies of erythrocyte and liver pyruvate kinase. Scand. J. Haematol. 16250.
Kahn, A., Kaplan, J.-C., and Dreyfus, J.-C. (1979). Advances in hereditary red cell enzyme anomalies. Hum. Genet. 501.
Krietsch, W. K. G., Krietsch, H., Kaiser, W., Dünnwald, M., Kuntz, G. W. K., Duhm, J., and Bücher, T. (1977). Hereditary deficiency of phosphoglycerate kinase: A new variant in erythrocytes and leucocytes, not associated with haemolytic anaemia. Eur. J. Clin. Invest. 7427.
Lalley, P. A., Minna, J. D., and Francke, U. (1978). Conservation of autosomal gene synteny groups in mouse and man. Nature 274160.
Lowry, O. H., Rosebrough, N. J., Farr, A. L., and Randall, R. J. (1951). Protein measurement with the Folin phenol reagent. J. Biol. Chem. 193265.
Miwa, S. (1973). Hereditary hemolytic anemia due to erythrocyte enzyme deficiency. Acta Haem. Jap. 36573.
Mohrenweiser, H. W. (1981). Frequency of enzyme deficiency variants in erythrocytes of newborn infants. Proc. Natl. Acad. Sci. USA 785046.
Moore, K. J., and Bulfield, G. (1981a). Genetic control of the expression of pyruvate kinase in different tissues of the mouse. Hereditas 9414.
Moore, K. J., and Bulfield, G. (1981b). An allele (Pk-1 b) from wild-caught mice that affects the activity and kinetics of erythrocyte and liver pyruvate kinase. Biochem. Genet. 19771.
Neel, J. V., Tiffany, T. O., and Anderson, N. G. (1973). Approaches to monitoring human populations for mutation rates and genetic disease. In Hollaender, A. (ed.), Chemical Mutagens, Vol. 3 Plenum Press, New York, pp. 105–150.
Neel, J. V., Mohrenweiser, H., Satoh, C., and Hamilton, H. B. (1979). A consideration of two biochemical approaches to monitoring human populations for a change in germ cell mutation rates. In Berg, K. (ed.). Genetic Damage in Man Caused by Environmental Agents Academic Press, New York, pp. 29–47.
Padua, R. A., Bulfield, G., and Peters, J. (1978). Biochemical genetics of a new glucosephosphate isomerase allele (Gpi-1 e) from wild mice. Biochem. Genet. 16127.
Paigen, K. (1981). Production of research mutants. ILAR News 2414.
Peters, J., Nash, H. R., Eicher, E. M., and Bulfield, G. (1981). Polymorphism of kidney pyruvate kinase in the mouse is determined by a gene, Pk-3, on chromosome 9. Biochem. Genet. 19757.
Pretsch, W., and Charles, D. J. (1983). Detection of enzyme mutants in mice by isoelectric focusing. Genet. Res. 41308.
Pretsch, W., Charles, D. J., and Narayanan, K. R. (1982). The agar contact replica technique after isoelectric focusing as a screening method for the detection of enzyme variants. Electrophoresis 3142.
Radola, B. J. (1980). Ultrathin-layer isoelectric focusing in 50–100 µm polyacrylamide gels on silanized glass plates or polyester films. Electrophoresis 143.
Rosa, R., Max-Audit, I., Izrael, V., Beuzard, Y., Thillet, J., and Rosa, J. (1981). Hereditary pyruvate kinase abnormalities associated with erythrocytosis. Am. J. Hematol. 1047.
Russell, W. L., Kelly, E. M., Hunsicker, P. R., Bangham, J. W., Maddux, S. C., and Phipps, E. L. (1979). Specific-locus test shows ethylnitrosourea to be the most potent mutagen in the mouse. Proc. Natl. Acad. Sci. USA 765818.
Searcy, G. P., Miller, D. R., and Tasker, J. B. (1971). Congenital hemolytic anaemia in the Basenji dog due to erythrocyte pyruvate kinase deficiency. Can. J. Comp. Med. 3567.
Valentine, W. N., Tanaka, K. R., and Miwa, S. (1961). A specific erythrocyte glycolytic enzyme defect (pyruvate kinase) in three subjects with congenital non-spherocytic hemolytic anemia. Trans. Assoc. Am. Phys. 74100.
Winchester, B. (1982). Animal models of human genetic diseases. Trends Biochem. Sci. 771.
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Charles, D.J., Pretsch, W. A new pyruvate kinase mutation with hyperactivity in the mouse. Biochem Genet 22, 1103–1117 (1984). https://doi.org/10.1007/BF00499635
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DOI: https://doi.org/10.1007/BF00499635