Ten kilobases of 5'-flanking region confers proper regulation of the mouse alcohol dehydrogenase-1 (Adh-1) gene in kidney and adrenal of transgenic mice.
The expression profile of the mouse Adh-1 gene, which encodes class I alcohol dehydrogenase enzyme (ADH), is complex and includes tissue specificity and differential hormone responsiveness. Whereas kidney Adh-1 transcription rate is stimulated six- to sevenfold by testosterone treatment, adrenal gland ADH-1 mRNA is reduced to less than 5% of control level within 18 h following hormone administration. Androgen receptor is required for both responses since neither occurs in Tfm mutant mice lacking receptor. Hormonal and tissue-specific aspects of Adh-1 regulation were studied in transgenic mice harboring either of two constructs containing either -2.5 kb or -10 kb of 5'-flanking sequence attached to an Adh-1 minigene. The minigene transcript was expressed in kidney and adrenal tissues, but not liver, in five independent lines harboring a transgene with -2.5 kb of 5'-flanking sequence. Androgen treatment repressed the level of the minigene transcript in adrenal gland, but did not cause induction in kidney. In four lines of transgenic mice carrying the construct with -10 kb of 5'-flanking sequence, the minigene transcript was both repressed in adrenal and induced in kidney by testosterone. These lines have no detectable transgene expression in liver tissue. The -10 kb region in the mouse Adh-1 gene contains necessary controlling regions for proper tissue expression and hormonal regulation in kidney and adrenal; however, this region does not contain all essential elements necessary for expression in liver.
Xie
D
D
Department of Biological Sciences, University of South Carolina, Columbia 29208, USA.
Narasimhan
P
P
Zheng
Y W
YW
Dewey
M J
MJ
Felder
M R
MR
D000311:Adrenal Glands / Q000378:metabolism*; D000426:Alcohol Dehydrogenase / Q000235:genetics*; D000818:Animals; D005260:Female; D015971:Gene Expression Regulation, Enzymologic; D007668:Kidney / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D011944:Receptors, Androgen / Q000502:physiology; D013739:Testosterone / Q000502:physiology
D011944:Receptors, Androgen; D013739:Testosterone; D000426:Alcohol Dehydrogenase