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. 1979 Sep;76(9):4526–4529. doi: 10.1073/pnas.76.9.4526

Genetics of type II glycogenosis: Assignment of the human gene for acid α-glucosidase to chromosome 17

Gian G D'Ancona 1, James Wurm 1, Carlo M Croce 1
PMCID: PMC411610  PMID: 388444

Abstract

We have studied somatic cell hybrids between thymidine kinase (EC 2.7.1.75) deficient mouse cells and human diploid fibroblasts for the expression of human acid α-glucosidase (EC 3.2.1.20). A deficiency in this enzyme is associated with the type II glycogenosis or Pompe disease. All 30 somatic cell hybrids selected in hypoxanthine/aminopterin/thymidine medium expressed human acid α-glucosidase and galactokinase (EC 2.7.1.6) and retained human chromosome 17; counterselection of the same hybrids in medium containing 5-bromodeoxyuridine resulted in the growth of hybrids that concordantly lost the expression of human acid α-glucosidase and galactokinase as well as human chromosome 17. Hybrids between thymidine kinase-deficient mouse cells and fibroblasts from a patient with Pompe disease that contained human chromosome 17 were found not to express human acid α-glucosidase. Because we have already shown that hybrids between mouse peritoneal macrophages and GM54VA simian virus 40-transformed human cells selectively retain human chromosome 17 and lose all other human chromosomes, we tested 13 independent mouse macrophage × GM54VA hybrid clones, including two that retained human chromosome 17 and no other human chromosomes, for the expression of human acid α-glucosidase and galactokinase. All 13 hybrid clones were found to express these human enzymes. Thus, we conclude that the gene coding for human acid α-glucosidase is located on human chromosome 17.

Keywords: cell hybrids, Pompe disease, hypoxanthine, aminopterin, thymidine selection, BrdUrd counterselection

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. BAUDHUIN P., HERS H. G., LOEB H. AN ELECTRON MICROSCOPIC AND BIOCHEMICAL STUDY OF TYPE II GLYCOGENOSIS. Lab Invest. 1964 Sep;13:1139–1152. [PubMed] [Google Scholar]
  2. Bannister D. L., Engel E. A G-like trisomy with a major 15 proximal supernumerary component derived from a D/E balanced maternal interchange. J Pediatr. 1975 Jun;86(6):916–917. doi: 10.1016/s0022-3476(75)80228-9. [DOI] [PubMed] [Google Scholar]
  3. Brown B. I., Brown D. H. The subcellular distribution of enzymes in type II glycogenosis and the occurrence of an oligo-alpha-1,4-glucan glucohydrolase in human tissues. Biochim Biophys Acta. 1965 Oct 25;110(1):124–133. doi: 10.1016/s0926-6593(65)80101-1. [DOI] [PubMed] [Google Scholar]
  4. Chern C. J. Detection of active heteropolymeric beta-glucuronidase in hybrids between mouse cells and human fibroblasts with beta-glucuronidase deficiency. Proc Natl Acad Sci U S A. 1977 Jul;74(7):2948–2952. doi: 10.1073/pnas.74.7.2948. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Chern C. J., Mellman W. J., Croce C. M. Assignment of the gene for cytoplasmic glutamic-oxaloacetic transaminase to the region q-24-qter of human chromosome 10. Somatic Cell Genet. 1976 Mar;2(2):177–182. doi: 10.1007/BF01542630. [DOI] [PubMed] [Google Scholar]
  6. Cicurel L., Croce C. M. Somatic cell hybrids between mouse peritoneal macrophages and SV40-transformed human cells. III. Identification of surface antigens coded for by human chromosomes 7 and 17. J Immunol. 1977 Jun;118(6):1951–1956. [PubMed] [Google Scholar]
  7. Croce C. M. Assignment of the integration site for simian virus 40 to chromosome 17 in GM54VA, a human cell line transformed by simian virus 40. Proc Natl Acad Sci U S A. 1977 Jan;74(1):315–318. doi: 10.1073/pnas.74.1.315. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Croce C. M., Kieba I., Koprowski H. Unidirectional loss of human chromosomes in rat-human hybrids. Exp Cell Res. 1973 Jun;79(2):461–463. doi: 10.1016/0014-4827(73)90470-9. [DOI] [PubMed] [Google Scholar]
  9. Croce C. M., Knowles B. B., Koprowski H. Preferential retention of the human chromosome C-7 in human-(thymidine kinase deficient) mouse hybrid cells. Exp Cell Res. 1973 Dec;82(2):457–461. doi: 10.1016/0014-4827(73)90366-2. [DOI] [PubMed] [Google Scholar]
  10. Jeffrey P. L., Brown D. H., Brown B. I. Studies of lysosomal alpha-glucosidase. I. Purification and properties of the rat liver enzyme. Biochemistry. 1970 Mar 17;9(6):1403–1415. doi: 10.1021/bi00808a015. [DOI] [PubMed] [Google Scholar]
  11. LEJEUNE N., THINES-SEMPOUX D., HERS H. G. Tissue fractionation studies. 16. Intracellular distribution and properties of alpha-glucosidases in rat liver. Biochem J. 1963 Jan;86:16–21. doi: 10.1042/bj0860016. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. LITTLEFIELD J. W. SELECTION OF HYBRIDS FROM MATINGS OF FIBROBLASTS IN VITRO AND THEIR PRESUMED RECOMBINANTS. Science. 1964 Aug 14;145(3633):709–710. doi: 10.1126/science.145.3633.709. [DOI] [PubMed] [Google Scholar]
  13. McBreen P., Engel E., Croce C. M. Assignment of the gene for glyoxalase I to region p21 leads to pter of human chromosome 6. Cytogenet Cell Genet. 1977;19(4):208–214. doi: 10.1159/000130810. [DOI] [PubMed] [Google Scholar]
  14. Norden A. G., O'Brien J. S. An electrophoretic variant of beta-galactosidase with altered catalytic properties in a patient with GM1 gangliosidosis. Proc Natl Acad Sci U S A. 1975 Jan;72(1):240–244. doi: 10.1073/pnas.72.1.240. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Nyhan W. L., Bakay B., Connor J. D., Marks J. F., Keele D. K. Hemizygous expression of glucose-6-phosphate dehydrogenase in erythrocytes of heterozygotes for the Lesch-Nyhan syndrome. Proc Natl Acad Sci U S A. 1970 Jan;65(1):214–218. doi: 10.1073/pnas.65.1.214. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Orkwiszewski K. G., Tedesco T. A., Croce C. M. Assignment of the human gene for galactokinase to chromosome 17. Nature. 1974 Nov 1;252(5478):60–62. doi: 10.1038/252060a0. [DOI] [PubMed] [Google Scholar]
  17. Radola B. J. Thin-layer isoelectric focusing of proteins. Biochim Biophys Acta. 1969 Nov 11;194(1):335–338. doi: 10.1016/0005-2795(69)90214-1. [DOI] [PubMed] [Google Scholar]
  18. Rattazzi M. C., Marks J. S., Davidson R. G. Electrophoresis of arylsulfatase from normal individuals and patients with metachromatic leukodystrophy. Am J Hum Genet. 1973 May;25(3):310–316. [PMC free article] [PubMed] [Google Scholar]
  19. Santachiara A. S., Nabholz M., Miggiano V., Darlington A. J., Bodmer W. Genetic analysis with man-mouse somatic cell hybrids. Linkage between human lactate dehydrogenase B and peptidase B genes. Nature. 1970 Jul 18;227(5255):248–251. doi: 10.1038/227248a0. [DOI] [PubMed] [Google Scholar]
  20. Seabright M. A rapid banding technique for human chromosomes. Lancet. 1971 Oct 30;2(7731):971–972. doi: 10.1016/s0140-6736(71)90287-x. [DOI] [PubMed] [Google Scholar]
  21. Siminovitch L. On the nature of hereditable variation in cultured somatic cells. Cell. 1976 Jan;7(1):1–11. doi: 10.1016/0092-8674(76)90249-x. [DOI] [PubMed] [Google Scholar]
  22. Swallow D. M., Corney G., Harris H., Hirschhorn R. Acid alpha-glucosidase: a new polymorphism in man demonstrable by 'affinity' electrophoresis. Ann Hum Genet. 1975 May;38(4):391–406. doi: 10.1111/j.1469-1809.1975.tb00629.x. [DOI] [PubMed] [Google Scholar]
  23. Willecke K., Lange R., Krüger A., Reber T. Cotransfer of two linked human genes into cultured mouse cells. Proc Natl Acad Sci U S A. 1976 Apr;73(4):1274–1278. doi: 10.1073/pnas.73.4.1274. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. van CREVELD The clinical course of glycogen disease. Can Med Assoc J. 1963 Jan 5;88:1–15. [PMC free article] [PubMed] [Google Scholar]

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