Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C1332347 (ADH)
 2,230 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The main ethanol-active alcohol dehydrogenase (ADH; alcohol:NAD+ oxidoreductase, EC 1.1.1.1) in mouse liver (ADH-AA) is similar in catalytic and molecular properties to horse liver ADH-EE and to the human class I ADHs. We have isolated cDNA clones encoding the entire mouse liver enzyme plus flanking regions. A mixture of 16 different oligonucleotides, each 14 bases long, was used to screen a liver cDNA library made from a DBA/2J mouse. A strongly hybridizing clone was found and identified as an ADH-encoding cDNA by partial DNA sequencing. This clone was used as a probe to identify others. Two overlapping cDNA clones together contained the entire protein-encoding region plus 100 nucleotides of the 5' noncoding region and 133 nucleotides of the 3' noncoding region culminating in a short poly(dA) tail. The amino acid sequence of the mouse liver enzyme deduced from this cDNA closely resembles that of horse liver ADH-E: 316 of 374 residues are identical, and 29 of the differences are conservative substitutions. The 5' region of this cDNA is interesting: the AUG that initiates the ADH polypeptide is preceded by an AUG that would encode the first amino acid of a tripeptide. Presumably termination of this tripeptide is followed by reinitiation at the AUG immediately preceding the sequence of the mature ADH polypeptide.
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PMID:Cloning and sequencing of cDNA encoding the complete mouse liver alcohol dehydrogenase. 315 87

The expression of the mouse Adh-1 gene which encodes the ADH-AA isoenzyme of liver alcohol dehydrogenase is under genetic control. The content of alcohol dehydrogenase in the C57BL inbred strain of mice is about twice that in DBA mice. In order to examine the mechanism for control of liver alcohol dehydrogenase expression in mice, we have isolated liver RNA from high and low enzyme activity strains and quantified the content of ADH mRNA with the ADH-A cDNA that was recently cloned in our laboratory. The content of ADH-A mRNA in liver correlates well with enzyme activity in the mouse strains; hence, the expression of Adh-1 appears to be under transcriptional control. A restriction fragment polymorphism was found in mouse liver DNA which correlates with the content of ADH-AA in the high and low ADH activity strains.
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PMID:Genetic control of liver alcohol dehydrogenase expression in inbred mice. 342 72

The ethanol-active alcohol dehydrogenase (ADH-A2) expressed at high levels in mouse liver is encoded by the Adh-1 gene. Inbred strains differ in the amount of ADH-A2 expressed. We report here the cloning and sequencing of the Adh-1 genes from mouse strains that express high and low amounts of ADH-A2 in liver (strains YBR/Ki and Balb/c respectively). The gene contains nine exons, and encodes an ADH-A subunit identical to that encoded by the cDNA isolated from DBA/2J, a strain with low liver ADH activity. This demonstrates that the difference between strains in liver ADH activity is not due to differences in the amino acid sequence of the ADH-A2. The 5'-nontranslated region and at least the first 225 bp 5' to the transcriptional start point are identical in both strains. We have found restriction fragment length polymorphisms in the Adh-1 gene that correlate with the level of expression of ADH-A2 in different strains. One of these RFLPs is within a remarkably long (288 bp) strictly alternating purine-pyrimidine sequence located in the first intron. This region in YBR/Ki contains 25 copies of the sequence ATGT(A/G)T (four of them inverted), which closely resembles important elements in the SV40 enhancer region. Balb/c mice, which express Adh-1 at lower levels, have a deletion that removes 101 bp of this sequence and also have several transition mutations; the comparable region has nine fewer ATGT(A/G)T repeats. These results suggest that the difference in gene expression may be due to differences in these hexamers or in other portions of the alternating purine-pyrimidine sequences, rather than in cis-acting sequences in the proximal 5' (promoter) region.
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PMID:Structure of the mouse Adh-1 gene and identification of a deletion in a long alternating purine-pyrimidine sequence in the first intron of strains expressing low alcohol dehydrogenase activity. 342 12

Southern blot analysis of mouse genomic DNA reveals two EcoRI fragments which faintly hybridize to mouse Adh-1 cDNA and are not part of the Adh-1 gene. These fragments were isolated from agarose gels, cloned, and characterized. Sequence analysis of the 2.1-kb EcoRI fragment suggests that it is likely a pseudogene since it does not contain a long open reading frame. However; the 2.0-kb EcoRI fragment contains a coding sequence with a long open reading frame which corresponds to exon 6 of the mouse Adh-1 gene. Comparison of the coding sequence with other known ADHs suggests that the sequence has diverged sufficiently from any currently known class of ADH to be a possible distinct class. Further confirmation awaits analysis of currently available genomic clones. Using these sequences as probe, restriction fragment length polymorphisms were identified for each sequence between C57Bl/6J and DBA/2J inbred mouse strains. The strain distribution pattern for these allelic differences was determined among the B x D recombinant inbred strains. This analysis revealed that the 2.1-kb EcoRI sequence is located on chromosome 3 but at a distance from the Adh-1/Adh-3 complex as previously reported. However, the new polymorphism identified in the 2.0-kb EcoRI fragment enabled this sequence to be mapped at the Adh-1/Adh-3 complex.
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PMID:Genetic mapping of a possible new alcohol dehydrogenase sequence to mouse chromosome 3 at the Adh-1/Adh-3 complex. 924 35