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Androgen Responsiveness of Mouse Kidney ß-Glucuronidase Requires 5'-Flanking and Intragenic Gus-s Sequences

Graduate Program in Developmental Biology (S.T., D.W.T.) College of Medicine University of Cincinnati Cincinnati, Ohio 45221
Children’s Hospital Research Foundation (P.M.G., R.E.G.) Cincinnati, Ohio 45229

Genetics studies of natural variants of the androgen response of mouse ß-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.

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