Open AccessAdenosine deaminase (ADA) deficiency in cells derived from humans with severe combined immunodetficiency is due to an aberration of the ADA protein
Author(s) -
D. Valerio,
M. G. C. Duyvesteyn,
H. van Ormondt,
P. Meera Khan,
A. J. Van Der Eb
Publication year - 1984
Publication title -
nucleic acids research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 9.008
H-Index - 537
eISSN - 1362-4954
pISSN - 0305-1048
DOI - 10.1093/nar/12.2.1015
Subject(s) - adenosine deaminase , biology , adenosine deaminase deficiency , microbiology and biotechnology , severe combined immunodeficiency , gene , protein biosynthesis , complementary dna , messenger rna , cell culture , gene expression , adenosine , genetics , biochemistry
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.