Androgen responsiveness of mouse kidney beta-glucuronidase requires 5'-flanking and intragenic Gus-s sequences.
Genetics studies of natural variants of the androgen response of mouse beta-glucuronidase (GUS) reveal a cis-active element closely linked to the GUS structural gene (Gus-s) that is necessary for this kidney-specific response. Results of our previous studies suggested sequences within or near an androgen-inducible deoxyribonuclease I-hypersensitive site (DH site) located in the ninth intron of Gus-s are associated with the androgen response of GUS. Using transgenic mice, we now demonstrate that at least two regions of sequence within Gus-s are involved in regulating the androgen response of GUS. The first, located within 3.8 kb of Gus-s 5'-flanking sequence, directs the response and its tissue specificity, while the second, located within a 6.4-kb fragment of Gus-s extending from the third through the ninth intron of Gus-s, protects the androgen responsiveness of the transgene from repressive influences of the insertion site.
Thornton
S
S
Graduate Program in Developmental Biology, College of Medicine, University of Cincinnati, Ohio 45221, USA.
Thomas
D W
DW
Gallagher
P M
PM
Ganschow
R E
RE
D000728:Androgens / Q000378:metabolism / Q000494:pharmacology*; D000818:Animals; D005260:Female; D005786:Gene Expression Regulation; D017930:Genes, Reporter; D005966:Glucuronidase / Q000187:drug effects / Q000235:genetics* / Q000378:metabolism*; D007438:Introns; D007668:Kidney / Q000187:drug effects / Q000201:enzymology*; D008156:Luciferases / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008809:Mice, Inbred C3H; D008815:Mice, Inbred Strains; D008822:Mice, Transgenic; D012045:Regulatory Sequences, Nucleic Acid; D019076:Transgenes
D000728:Androgens; D008156:Luciferases; D005966:Glucuronidase