Summary
The structural gene encoding human δ-aminolevulinate dehydratase has been assigned to the long arm of chromosome 9 by somatic cell hybridization techniques using murine erythroleukemia-human fibroblast somatic cell hybrids. Dimethyl sulfoxide induction of erythroid differentiation in these hybrid cells resulted in a 3 to 12-fold increase in the levels of total δ-aminolevulinate dehydratase. Human δ-aminolevulinate dehydratase was detected by an immunodiscrimination assay using polyclonal mouse anti-human δaminolevulinate dehydratase antibodies. Of four primary hybrid clones, each from an independent fusion, one hybrid line, XX-8, was positive for human δ-aminolevulinate dehydratase. Examination of 23 secondary, tertiary, and quaternary XX-8 subclones revealed that the expression of the human isozyme segregated with human chromosome 9q, confirming the provisional regional assignment made by classical linkage studies. One positive quaternary clone, XX-8-H21-H7-2, expressed human δ-aminolevulinate dehydratase activity and contained only human 9q13»qter. In addition, studies of tetiary and quaternary subclones from two series, XX-8-A31 and XX-8-H21-H7, indicated that murine regulatory factors increased the human as well as the murine enzymatic activity following induction of erythroid differentiation.
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References
Anderson PM, Densick RJ (1979) Purification and properties of δ-aminolevulinate dehydratase from human erythrocytes. J Biol Chem 254:6924–6930
Anderson PM, Desnick RJ (1980) Purification and properties of uroporphyrinogen I synthase from human erythrocytes. J Biol Chem 255:1993–1999
Axelrod DE, Gopalkrishnan TV, Willing M, Anderson WF (1978) Maintenance of hemoglobin inducibility in somatic cell hybrids of tetraploid (2S) mouse erythroleukemia cells with mouse or human fibroblasts. Somatic Cell Genet 4:157–168
Beaumont C, Foubert C, Grandchamp B, Weil D, Van Cong N, Gross M-S, Nordmann Y (1984) Assignment of the human gene for δ-aminolevulinate dehydratase to chromosome 9 by somatic cell hybridization and specific enzyme immunoassay. Ann Hum Genet 48:153–159
de Verneuil H, Grandchamp B, Foubert C, Weil D, N'Guyen VC, Gross M-S, Sassa S, Nordmann Y (1984) Assignment of the gene for uroporphyrinogen decarboxylase to human chromosome 1 by somatic cell hybridization and specific enzyme immunoassay. Hum Genet 66:202–205
Eiberg H, Mohr J, Nielsen LS (1983) δ-Aminolevulinate dehydratase: synteny with AB0-AKI-ORM (and assignment to chromosome 9). Clin Genet 23:150–154
Giampietro PF, Desnick RJ (1983) Determination of δ-aminolevulinate dehydratase activity by a specific fluorometric coupledenzyme assay. Anal Biochem 131:83–92
Grandchamp B, Weil D, Nordmann Y, Van Cong N, de Verneuil H, Foubert C, Gross M-S (1983) Assignment of the human coproporphyrinogen oxidase to chromosome 9. Hum Genet 64:180–183
Kappas A, Sassa S, Anderson KE (1983) The porphyrias. In: Stanbury JB, Wyngaarden JB, Frederickson DS, Goldstein JL, Brown MS (eds). The metabolic basis of inherited disease. McGraw-Hill Book Co, New York, pp 1301–1384
Meera Kahn P, Smith M (1984) Report of the committee on the genetic constitution of chromosomes 7, 8, and 9. Cytogenet Cell Genet 37:71–102
Peterson JL, McConkey EH (1976) Proteins of Friend leukemia cells. Comparison of hemoglobin-synthesizing and noninduced populations. J Biol Chem 251:555–558
Sassa S (1976) Sequential induction of heme enzymes during erythroid differentiation of mouse Friend leukemia virus-infected cells. J Exp Med 143:305–315
Schuchman EH, Astrin KH, Aula P, Desnick RJ (1984) Regional assignment of the structural gene for human α-L-iduronidase. Proc Natl Acad Sci USA 81:1169–1173
Wang A-L, Arredondo-Vega FX, Giampietro PF, Smith M, Anderson WF, Desnick RJ (1981) Regional gene assignment of human porphobilinogen deaminase and esterase A4 to chromosome 11q23»11qter. Proc Natl Acad Sci USA 78:5734–5738
Willing M, Neinhuis A, Anderson WF (1979) Selective activation of human β-but not γ-globin gene in human fibroblast and mouse erythroleukemia cell hybrids. Nature 277:534–538
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Wang, A.L., Astrin, K.H., Anderson, W.F. et al. δ-Aminolevulinate dehydratase: Induced expression and regional assignment of the human gene to chromosome 9q13»qter. Hum Genet 70, 6–10 (1985). https://doi.org/10.1007/BF00389449
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DOI: https://doi.org/10.1007/BF00389449