Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.5.4.4 (adenosine deaminase)
 5,136 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The promoter of the human gene for adenosine deaminase (ADA) is extremely G/C-rich, contains several G/C-box motifs (GGGCGGG) and lacks any apparent TATA or CAAT boxes. These features are commonly found in promoters of genes that lack a strong tissue specificity, and are referred to as "housekeeping genes". Like other housekeeping genes, the ADA gene is expressed in all tissues. However, there is a considerable variation in the levels of expression of the ADA protein in different tissues. In order to study the activity of the ADA promoter, transgenic mice were generated that harbor a chimeric gene composed of the ADA promoter linked to a reporter gene encoding the bacterial enzyme Chloramphenicol Acetyl Transferase (CAT). These mice reproducibly showed CAT expression in all tissues examined, including the hemopoietic organs (spleen, thymus and bone marrow). However, examination of the actual cell types expressing the CAT gene revealed the ADA promoter to be inactive in the hemopoietic cells. This was substantiated by a transplantation experiment in which bone marrow from ADA-CAT transgenic mice was used to reconstitute the hemopoietic compartment of lethally irradiated mice. The engrafted recipients revealed strongly reduced CAT activity in their hemopoietic organs. The lack of expression in hemopoietic cells was further shown to be correlated with a hypermethylated state of the transgene. Combined, our data suggest that the ADA promoter sequences tested can direct expression in a wide variety of tissues as expected for a regular housekeeping gene promoter. However, the activity of the ADA promoter fragment did not reflect the tissue-specific variations in expression levels of the endogenous ADA gene. Additionally, regulatory elements are needed for expression in the hemopoietic cells.
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PMID:Activity of the adenosine deaminase promoter in transgenic mice. 305 38

The housekeeping enzyme adenosine deaminase (ADA) shows a large variation in tissue-specific expression ranging from 1 Iu in red blood cells to 880 Iu in thymocytes. We investigated the acute lymphocytic leukemic cell line Molt-4 (660 Iu ADA/g protein) and the promyelocytic cell line HL-60 (38 Iu ADA/g protein) as a model system to determine the levels at which the tissue-specific expression of ADA is regulated. From our results it can be concluded that the almost 20-fold difference in ADA expression between Molt-4 and HL-60 is the result of differences in the post-transcriptional processing and/or stability of ADA pre-mRNA within the nucleus.
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PMID:Adenosine deaminase gene expression is regulated posttranscriptionally in the nucleus. 316 99

We have investigated the structural gene for adenosine deaminase (ADA) in a female infant with ADA deficiency associated severe combined immune deficiency (ADA-SCID) disease and her family by DNA restriction-fragment-length analysis. In this family a new ADA-specific restriction-fragment-length variant was detected, which involves a 3.2-kb deletion spanning the ADA promoter as well as the first exon. It was found that the patient, who was born to a consanguineous couple, was homozygous and both her parents and her brother were heterozygous for the deletion. No ADA-specific mRNA could be detected by hybridization in fibroblasts derived from this patient. Thus the patient was established to be homozygous for a true null ADA allele. In the light of the apparently normal development of most tissues except the lymphoid tissue the above finding directly questions the classification of ADA as a 'housekeeping' enzyme.
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PMID:Severe combined immune deficiency due to a homozygous 3.2-kb deletion spanning the promoter and first exon of the adenosine deaminase gene. 368 97

A new immunoextraction method using biotinylated antibodies and streptavidin-coated magnetic beads has been developed and applied to study the repair of uv-induced DNA damage in specific DNA sequences. uv-irradiated cells were allowed to carry out DNA repair for various time intervals in the presence of 5-bromodeoxyuridine (BrdU). Purified and restricted DNA was subjected to an immunoextraction method employing an anti-BrdU antibody (alpha Brdu), biotinylated goat antimouse antibodies (G alpha Mbio), and streptavidin-coated polymeric magnetic beads. Separation of BrdU containing DNA was achieved by using a magnetic device. This extraction procedure resulted in two fractions of DNA, i.e., BrdU-containing and non-BrdU-containing DNA. Both fractions were blotted on filters and subsequently hybridized with specific DNA probes to determine the relative amount of defined fragments in the two fractions of DNA. Repair experiments using normal primary human fibroblasts showed no difference in the incorporation of repair label in the active adenosine deaminase gene and the inactive 754 locus during the first 4 h following uv irradiation. After longer repair times the active gene incorporated more repair label than the inactive gene, consistent with the known preferential repair of cyclobutane pyrimidine dimers from active housekeeping genes.
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PMID:The use of streptavidin-coated magnetic beads and biotinylated antibodies to investigate induction and repair of DNA damage: analysis of repair patches in specific sequences of uv-irradiated human fibroblasts. 845 14

The transition between dependence on maternal transcripts and proteins inherited in the oocyte and embryonic gene expression in the human preimplantation embryo occurs at the four- to eight-cell stage. Recently, studies using reverse transcriptase polymerase chain reaction (RT-PCR) have detected paternal transcripts for the Y-linked genes, ZFY and SRY, and the myotonic dystrophy associated protein kinase gene, DK, as early as the late pronucleate one-cell stage. However, expression at the protein level has not been demonstrated and its function at these early stages is unknown. Using coding sequence polymorphisms to distinguish maternal and paternal transcripts, we have examined the transcription of two ubiquitously expressed genes: X-linked glucose-6-phosphate dehydrogenase (G6PD) and adenosine deaminase (ADA). Both G6PD and ADA are housekeeping genes with TATA-less promoters which, because of their roles in metabolism and ubiquitous expression, may provide a more reliable indication of the timing of activation of the embryonic genome. They also each have biallelic polymorphisms with a high heterozygosity ratio which can be detected by restriction digestion. Couples undergoing in vitro fertilization (IVF) were screened for these polymorphisms. Individual spare oocytes and embryos at different stages of preimplantation development were analyzed by RT-PCR and appropriate restriction digestion in those cases in which the male partner carried a different allele to the female partner. In addition, since only female embryos inherit the paternal allele of X-linked G6PD, cDNA was also analyzed for ZFX/ZFY transcripts to identify the sex of each embryo. One hundred and twenty three individual oocytes and embryos were analyzed by RT-PCR and restriction digestion to detect the paternal transcripts from the polymorphic alleles. Maternal transcripts for G6PD, ADA, and ZFX were detected in all oocytes and embryos and at all stages. Following restriction digestion, paternal G6PD and ZFY transcripts were first detected at the four-cell stage and paternal ADA transcripts in an embryo at the three-cell stage coinciding with the onset of dependency on transcription from the embryonic genome. This approach should be widely applicable to other genes since similar polymorphisms exist in the coding regions of many genes.
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PMID:Paternal transcripts for glucose-6-phosphate dehydrogenase and adenosine deaminase are first detectable in the human preimplantation embryo at the three- to four-cell stage. 936 38