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Phosphorylase kinase deficiency in I–strain mice is associated with a frameshift mutation in the α subunit muscle isoform

Nature Genetics volume 5, pages 381–385 (1993)Cite this article

Abstract

Heritable phosphorylase kinase (Phk) deficiency underlies a group of glycogenoses in humans, mice and rats that differ in mode of inheritance and tissue–specificity. It is assumed that this heterogeneity is caused by mutations affecting different subunits and isoforms of Phk. As the first Phk deficiency mutation to be identified, we report a single–nucleotide insertion in the coding sequence of the Phk α subunit muscle isoform of the I–strain mouse. This mutation accounts for the virtually complete enzymatic deficiency, the tissue specificity and the X–linked mode of inheritance in this mutant.

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References

  1. Picket-Gies, C.R. & Walsh, D.A. Phosphorylase kinase. In The Enzymes 17 (eds Boyer, P.O. & Krebs, E.G.) 395–459 (Academic Press, Orlando, 1986).

    Google Scholar 

  2. Huijing, F. & Fernandes, J. X-chromosomal inheritance of liver glycogenosis with phosphorylase kinase deficiency. Am. J. hum. Genet. 21, 275–284 (1969).

    CAS  PubMed  PubMed Central  Google Scholar 

  3. Schimke, R.N., Zakheim, R.M., Corder, R.C. & Hug, G. Glycogen storage disease type IX: benign glycogenosis of liver and hepatic phosphorylase kinase deficiency. J. Pediatr. 83, 1031–1034 (1973).

    Article  CAS  Google Scholar 

  4. De Bruijn, W.C., Fernandes, J.F., Huber, J. & Coster, J.F. Liver glycogenosis. A biochemical and ultrastructural study. Path. Eur. 10, 3–15 (1975).

    CAS  Google Scholar 

  5. Lederer, B., Van Hoof, F., Van Den Berghe, G. & Hers, H.G. Glycogen phosphorylase and its converter enzymes in hemolysates of normal human subjects and of patients with type VI glycogen storage disease. A study of phosphorylase kinase deficiency. Biochem. J. 147, 23–35 (1975).

    Article  CAS  Google Scholar 

  6. Alvarado, L.J.F., Gasca-Centebo, E. & Grier, R.E. Hepatic phosphorylase β kinase deficiency with normal enzyme activity in leukocytes. J. Pediatr. 113, 865–867 (1988).

    Article  CAS  Google Scholar 

  7. Shin, Y.S. Diagnosis of glycogen storage disease. J. inher. metab. Dis. 13, 19–434 (1990).

    Article  Google Scholar 

  8. Bakker, H.D., Taminiau, J.A.J.M., Van Den Berg, J.E.T. & Berger, R. Hepatic phosphorylase b kinase deficiency with normal enzyme activity in leukocytes and erythrocytes. J. inher. metab. Dis. 14, 269–270 (1991).

    Article  CAS  Google Scholar 

  9. Hug, G., Schubert, W.K. & Chuck, G. Phosphorylase kinase of the liver: deficiency in a girl with increased hepatic glycogen. Science 153, 1534–1535 (1966).

    Article  CAS  Google Scholar 

  10. Lederer, B., Van De Werve, G., De Barsy, Th. & Hers, H.G. The autosomal form of phosphorylase kinase deficiency in man: reduced activity of the muscle enzyme. Biochem. biophys. Res. Commun. 92, 169–174 (1980).

    Article  CAS  Google Scholar 

  11. Lerner, A., Iancu, T.C., Bashan, N., Potashnik, R. & Moses, S. A new variant of glycogen storage disease. Type IXc. Am. J. dis. Child. 136, 406–410 (1982).

    Article  CAS  Google Scholar 

  12. Madlom, M., Besley, G.T.N., Cohen, P.T.W. & Marrian, V.J. Phosphorylase b kinase deficiency in a boy with glycogenosis affecting both liver and muscle. Eur. J. Pediatr. 149, 52–53 (1989).

    Article  CAS  Google Scholar 

  13. Ohtani, Y., Matsuda, I., Iwamasa, T., Tamari, H., Origuchi, Y. & Miike, T. Infantile glycogen storage myopathy in a girl with phosphorylase kinase deficiency. Neurology 32, 833–838 (1982).

    Article  CAS  Google Scholar 

  14. Abarbanel, J.M., Bashan, N., Potashnik, R., Osimani, A., Moses, S.W. & Herishanu, Y. Adult muscle phosphorylase b kinase deficiency. Neurology 36, 560–562 (1986).

    Article  CAS  Google Scholar 

  15. Clemens, P.R., Yamamoto, M. & Engel, A.G. Adult phosphorylase b kinase deficiency. Ann. Neurol. 28, 529–538 (1990).

    Article  CAS  Google Scholar 

  16. Eishi, Y., Takemura, T., Sone, R., Yamamura, H., Narisawa, K., Ichinohasama, R., Tanaka, M. & Hatakeyama, S. Glycogen storage disease confined to the heart with deficient activity of cardiac phosphorylase kinase: a new type of glycogen storage disease. Hum. Pathol. 16, 193–197 (1985).

    Article  CAS  Google Scholar 

  17. Servidei, S., Metlay, L.A., Chodosh, J. & DiMauro, S. Fatal infantile cardiopathy caused by phosphorylase b kinase deficiency. J. Pediatr. 113, 82–85 (1988).

    Article  CAS  Google Scholar 

  18. Lyon, J.B. Muscle and liver glycogen levels in lean and obese strains of mice. Am. J. Physiol. 190, 434–438 (1957).

    CAS  PubMed  Google Scholar 

  19. Lyon, J.B. The X chromosome and the enzymes controlling muscle glycogen: Phosphorylase kinase. Biochem. Genet. 4, 169–185 (1970).

    Article  CAS  Google Scholar 

  20. Cohen, P.T.W. & Cohen, P. The molecular basis of muscle phosphorylase kinase deficiency in I-strain mice. In Carbohydrate Metabolism and its Disorders, Vol. 3 (eds Randle, P.J. et al.) 119–138 (Academic Press, New York, 1981).

    Google Scholar 

  21. Varsanyi, M., Vrbica, A. & Heilmeyer, L.M.G. X-linked dominant inheritance of partial phosphorylase kinase deficiency in mice. Biochem. Genet. 18, 247–261 (1980).

    Article  CAS  Google Scholar 

  22. Malthus, R., Clark, D.G., Watts, C. & Sneyd, J.G.T. Glycogen-storage disease in rats, a genetically determined deficiency of liver phosphorylase kinase. Biochem. J. 188, 99–106 (1980).

    Article  CAS  Google Scholar 

  23. Davidson, J.J., Özçelik, T., Hamacher, C., Willems, P.J., Francke, U. & Kilimann, M.W. cDNA cloning of a liver isoform of the phosphorylase kinase α subunit and mapping of the gene to Xp22.2-p22.1, the region of human X-linked liver glycogenosis. Proc. natn. Acad. Sci. U.S.A. 89, 2096–2100 (1992).

    Article  CAS  Google Scholar 

  24. Calalb, M.B., Fox, D.T. & Hanks, S.K. Molecular cloning and enzymatic analysis of the rat homolog of ‘PhK-γ’, an isoform of phosphorylase kinase catalytic subunit. J. biol. Chem. 267, 1455–1463 (1992).

    CAS  PubMed  Google Scholar 

  25. Francke, U., Darras, B.T., Zander, N.F. & Kilimann, M.W. Assignment of human genes for phosphorylase kinase subunits χ (PHKA) to Xq12-q13 and β (PHKB) to 16q12-q13. Am. J. hum. Genet. 45, 276–282 (1989).

    CAS  PubMed  PubMed Central  Google Scholar 

  26. Chamberlain, J.S., VanTuinen, P., Reeves, A.A., Philip, B.A. & Caskey, C.T. Isolation of cDNA clones for the catalytic γ subunit of mouse muscle phosphorylase kinase: Expression of mRNA in normal and mutant Phk mice. Proc. natn. Acad. Sci. U.S.A. 84, 2886–2890 (1987).

    Article  CAS  Google Scholar 

  27. Jones, T.A., da Cruz e Silva, E.F., Spurr, N.K., Sheer, D. & Cohen, P.T.W. Localisation of the gene encoding the catalytic γ subunit of phosphorylase kinase to human chromosome bands 7p12–q21. Biochim. Biophys. Acta 1048, 24–29 (1990).

    Article  CAS  Google Scholar 

  28. Harmann, B., Zander, N.F. & Kilimann, M.W. Isoform diversity of phosphorylase kinase α and β subunits generated by alternative RNA splicing. J. biol. Chem. 266, 15631–15637 (1991).

    CAS  PubMed  Google Scholar 

  29. Wüllrich, A., Hamacher, C., Schneider, A. & Kilimann, M.W. The multiphosphorylation domain of the phosphorylase kinase αM and αL subunits is a hotspot of differential mRNA processing and of molecular evolution. J. biol. Chem. 268, 23208–23214 (1993).

    PubMed  Google Scholar 

  30. Barnard, P.J., Derry, J.M.J., Ryder-Cook, A.S., Zander, N.F. & Kilimann, M.W. Mapping of the phosphorylase kinase alpha subunit gene on the mouse X chromosome. Cytogenet. cell Genet. 53, 91–94 (1990).

    Article  CAS  Google Scholar 

  31. Huijing, F., Eicher, E.M. & Coleman, D.L. Location of phosphorylase kinase (Phk) in the mouse X chromosome. Biochem. Genet. 9, 193–196 (1973).

    Article  CAS  Google Scholar 

  32. Bender, P.K. & Lalley, P.A. I/Lyn mouse phosphorylase kinase deficiency: Mutation disrupts expression of the α/α′-subunit mRNAs. Proc. natn. Acad. Sci. U.S.A. 86, 9996–10000 (1989).

    Article  CAS  Google Scholar 

  33. Zander, N.F. et al. cDNA cloning and complete primary structure of skeletal muscle phosphorylase kinase (α subunit). Proc. natn. Acad. Sci. U.S.A. 85, 2929–2933 (1988).

    Article  CAS  Google Scholar 

  34. Wexler, I.D. et al. Heterogeneous expression of protein and mRNA in pyruvate dehydrogenase deficiency. Proc. natn. Acad. Sci. U.S.A. 85, 7336–7340 (1988).

    Article  CAS  Google Scholar 

  35. Kee, S.M. & Graves, D.J. Isolation and properties of the active γ subunit of phosphorylase kinase. J. biol. Chem. 261, 4732–4737 (1986).

    CAS  PubMed  Google Scholar 

  36. Mashima, Y. et al. Nonsense-codon mutations of the ornithine aminotransferase gene with decreased levels of mutant mRNA in gyrate atrophy. Am. J. hum. Genet. 51, 81–91 (1992).

    CAS  PubMed  PubMed Central  Google Scholar 

  37. Kilimann, M.W. et al. The α and β subunits of phosphorylase kinase are homologous: cDNA cloning and primary structure of the β subunit. Proc. natn. Acad. Sci. U.S.A. 85, 9381–9385 (1988).

    Article  CAS  Google Scholar 

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Authors and Affiliations

  1. Institut für Physiologische Chemie, Medizinische Fakultät, Ruhr-Universität Bochum, D-44780, Bochum, Germany

    Angela Schneider, Jutta J. Davidson, Andrea Wüllrich & Manfred W. Kilimann

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  1. Angela Schneider
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  2. Jutta J. Davidson
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  3. Andrea Wüllrich
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  4. Manfred W. Kilimann
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Schneider, A., Davidson, J., Wüllrich, A. et al. Phosphorylase kinase deficiency in I–strain mice is associated with a frameshift mutation in the α subunit muscle isoform. Nat Genet 5, 381–385 (1993). https://doi.org/10.1038/ng1293-381

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