Skip to main content
NCBI home page
Nucleic Acids Research logoLink to Nucleic Acids Research
. 1984 Jan 25;12(2):1015–1024. doi: 10.1093/nar/12.2.1015

Adenosine deaminase (ADA) deficiency in cells derived from humans with severe combined immunodeficiency is due to an aberration of the ADA protein.

D Valerio, M G Duyvesteyn, H van Ormondt, P Meera Khan, A J van der Eb
PMCID: PMC318552  PMID: 6198631

Abstract

In order to determine the molecular basis of adenosine deaminase (ADA) deficiency in cells derived from patients with severe combined immunodeficiency (SCID) disease, we used a human ADA cDNA clone (1) to analyse the organization and transcription of the ADA gene in both normal and ADA-SCID cells. In five lymphoblastoid ADA-SCID cell lines we could detect no deletions or rearrangements in the ADA gene and its flanking sequences. Furthermore, synthesis and processing of ADA mRNA appeared to be normal in the ADA-SCID cells, and ADA-specific mRNA from two ADA-SCID cells could be translated in vitro into a protein with the molecular weight of normal ADA; this protein, however, could hardly be precipitated with an ADA antiserum. The results indicate that in these two ADA-SCID cell lines, the lack of ADA activity is not due to transcriptional or translational defects, but to subtle changes in the configuration of the protein affecting both its enzymatic and immunological characteristics.

Full text

PDF
1015

Images in this article

1018Image
on p.1018
1019Image
on p.1019
1020Image
on p.1020

Selected References

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

  1. Adrian G. S., Hutton J. J. Adenosine deaminase messenger RNAs in lymphoblast cell lines derived from leukemic patients and patients with hereditary adenosine deaminase deficiency. J Clin Invest. 1983 Jun;71(6):1649–1660. doi: 10.1172/JCI110920. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Bernards R., Houweling A., Schrier P. I., Bos J. L., Van der Eb A. J. Characterization of cells transformed by Ad5/Ad12 hybrid early region I plasmids. Virology. 1982 Jul 30;120(2):422–432. doi: 10.1016/0042-6822(82)90042-3. [DOI] [PubMed] [Google Scholar]
  3. Daddona P. E. Human adenosine deaminase. Properties and turnover in cultured T and B lymphoblasts. J Biol Chem. 1981 Dec 10;256(23):12496–12501. [PubMed] [Google Scholar]
  4. Daddona P. E., Kelley W. N. Characteristics of an aminohydrolase distinct from adenosine deaminase in cultured human lymphoblasts. Biochim Biophys Acta. 1981 Apr 14;658(2):280–290. doi: 10.1016/0005-2744(81)90298-9. [DOI] [PubMed] [Google Scholar]
  5. Daddona P. E., Kelley W. N. Human adenosine deaminase. Purification and subunit structure. J Biol Chem. 1977 Jan 10;252(1):110–115. [PubMed] [Google Scholar]
  6. Giblett E. R., Anderson J. E., Cohen F., Pollara B., Meuwissen H. J. Adenosine-deaminase deficiency in two patients with severely impaired cellular immunity. Lancet. 1972 Nov 18;2(7786):1067–1069. doi: 10.1016/s0140-6736(72)92345-8. [DOI] [PubMed] [Google Scholar]
  7. Herbschleb-Voogt E., Scholten J. W., Meera Khan P. Basic defect in the expression of adenosine deaminase in ADA-SCID disease. II. Deficiency of ADA-CRM detected in heterozygote human-Chinese hamster cell hybrids. Hum Genet. 1983;63(2):121–125. doi: 10.1007/BF00291530. [DOI] [PubMed] [Google Scholar]
  8. Hirschhorn R., Beratis N., Rosen F. S. Characterization of residual enzyme activity in fibroblasts from patients with adenosine deaminase deficiency and combined immunodeficiency: evidence for a mutant enzyme. Proc Natl Acad Sci U S A. 1976 Jan;73(1):213–217. doi: 10.1073/pnas.73.1.213. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Hirschhorn R., Roegner V., Jenkins T., Seaman C., Piomelli S., Borkowsky W. Erythrocyte adenosine deaminase deficiency without immunodeficiency. Evidence for an unstable mutant enzyme. J Clin Invest. 1979 Oct;64(4):1130–1139. doi: 10.1172/JCI109552. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Martin D. W., Jr, Gelfand E. W. Biochemistry of diseases of immunodevelopment. Annu Rev Biochem. 1981;50:845–877. doi: 10.1146/annurev.bi.50.070181.004213. [DOI] [PubMed] [Google Scholar]
  11. Thompson L. F., Seegmiller J. E. Adenosine deaminase deficiency and severe combined immunodeficiency disease. Adv Enzymol Relat Areas Mol Biol. 1980;51:167–210. doi: 10.1002/9780470122969.ch4. [DOI] [PubMed] [Google Scholar]
  12. Uberti J., Peterson W. D., Jr, Lightbody J. J., Johnson R. M. A phenotypically normal revertant of an adenosine deaminase-deficient lymphoblast cell line. J Immunol. 1983 Jun;130(6):2866–2870. [PubMed] [Google Scholar]
  13. Wiginton D. A., Hutton J. J. Immunoreactive protein in adenosine deaminase deficient human lymphoblast cell lines. J Biol Chem. 1982 Mar 25;257(6):3211–3217. [PubMed] [Google Scholar]

Articles from Nucleic Acids Research are provided here courtesy of Oxford University Press

RESOURCES