Biochemical genetics of aldehyde reductase in the mouse: Ahr-1--a new locus linked to the alcohol dehydrogenase gene complex on chromosome 3.
Electrophoretic and activity variants for a liver aldehyde reductase (AHR-A2) among strains of Mus musculus have been used in genetic analyses to demonstrate close linkage between the locus encoding this enzyme (designated Ahr-1) and the alcohol dehydrogenase gene complex on chromosome 3. No recombinants were observed between Adh-3 (encoding alcohol dehydrogenase C2; ADH-C2) and Ahr-1 among 42 backcross animals. Moreover, linkage disequilibrium between these loci was observed among 58 of 60 strains of mice examined and among seven recombinant inbred strains derived from C57BL/6J and BALB/c mice. Liver hexonate dehydrogenase (HDH-A) was electrophoretically invariant among the strains examined. Gel filtration analyses demonstrated that AHR-A2 and HDH-A had native molecular weights of approximately 80,000 and 32,000, respectively. Three-banded allozyme patterns for AHR-A2 in CBA/H x castaneus hybrid animals were consistent with a dimeric subunit structure. Comparative substrate and coenzyme specificities for AHR-A2, HDH-A, and ADH-A2 (liver ADH isozyme) were examined. AHR-A2 exhibited a defined specificity toward p-nitrobenzaldehyde as substrate, whereas the other enzymes exhibited broad specificities toward various aliphatic, aromatic, and monosaccharide aldehydes. It is proposed that Ahr-1 is a product of a gene duplication event during mammalian evolution of the primordial mammalian Adh locus and that considerable divergence in catalytic properties has subsequently occurred.
D000426:Alcohol Dehydrogenase; D000429:Alcohol Oxidoreductases / Q000235:genetics*; D000483:Alleles; D000818:Animals; D002237:Carbohydrate Dehydrogenases / Q000235:genetics; D002874:Chromosome Mapping; D004588:Electrophoresis, Cellulose Acetate; D005260:Female; D008040:Genetic Linkage; D008099:Liver / Q000201:enzymology; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains / Q000235:genetics*; D008970:Molecular Weight; D014018:Tissue Distribution
D000429:Alcohol Oxidoreductases; D002237:Carbohydrate Dehydrogenases; D000426:Alcohol Dehydrogenase; C020590:L-glucuronate reductase; C019642:alcohol dehydrogenase (NADP+)