Tissue-specific genetic variation in the level of mouse alcohol dehydrogenase is controlled transcriptionally in kidney and posttranscriptionally in liver.
Tissue-specific genetic variation in expression of the alcohol dehydrogenase, encoded by the Adh-1 gene, is found between C57BL/6J (B6) mice and B6.S congenic mice. B6.S mice contain a variant Adh-1 allele derived from a wild Danish strain in a B6 genetic background. B6 mice have nearly twice the alcohol dehydrogenase activity in liver but less than half the activity in kidney as B6.S mice. These tissue-specific genetic changes in alcohol dehydrogenase expression are manifest at the level of Adh-1-encoded mRNA. The regulatory site(s) involved act cis in both kidney and liver. These strains also differ in the extent to which androgen induces mRNA encoded by kidney Adh-1, with androgen increasing these levels 17-fold and 7.4-fold in the B6 and B6.S kidney, respectively. To identify the regulatory mechanism(s) underlying this strain variation in Adh-1 transcription in the B6 and B6.S kidney, liver, and androgen-induced kidney. For both uninduced and induced kidney, a difference in the transcription rate alone accounts for the strain difference in mRNA concentration. In contrast, because the Adh-1 transcription rate in liver does not differ significantly between B6 and B6.S mice, strain-specific variation in posttranscriptional regulation must be operative. Taken together these results indicate that the variation in Adh-1 expression between B6 and B6.S mice results from changes in both transcriptional and posttranscriptional control, and these controls are differentially operative in kidney and liver.
Tussey
L
L
Department of Biological Sciences, University of South Carolina, Columbia 29208.
Felder
M R
MR
D000426:Alcohol Dehydrogenase / Q000235:genetics*; D000818:Animals; D005786:Gene Expression Regulation; D005796:Genes; D014644:Genetic Variation; D007668:Kidney / Q000201:enzymology*; D007700:Kinetics; D008099:Liver / Q000201:enzymology*; D008297:Male; D051379:Mice; D008805:Mice, Inbred A; D008810:Mice, Inbred C57BL; D009928:Organ Specificity; D012313:RNA / Q000235:genetics / Q000302:isolation & purification; D012323:RNA Processing, Post-Transcriptional; D012333:RNA, Messenger / Q000235:genetics; D014158:Transcription, Genetic
D012333:RNA, Messenger; D012313:RNA; D000426:Alcohol Dehydrogenase