Genetic control of levels of murine kidney glucuronidase mRNA in response to androgen.
A cis-acting genetic element, designated Gus-r, regulates the androgen-induced rates of murine glucuronidase (EC 3.2.1.31) synthesis in kidney tubule cells and is tightly linked to the glucuronidase structural gene, Gus-s. To investigate the molecular mechanism underlying this regulation, we have cloned a glucuronidase-specific cDNA sequence in plasmid pBR322. This cloned DNA has been utilized as a probe in blot hybridization analyses to determine whether the control of androgen responsiveness of kidney glucuronidase synthesis by Gus-r is exerted over the level or the translatability of glucuronidase mRNA. Three important observations emerged from these studies: (i) glucuronidase mRNA exists as a single size class of approximately 2,800 nucleotides; (ii) androgen stimulation of glucuronidase synthesis is directly related to the level of glucuronidase mRNA; and (iii) strain differences in levels of kidney glucuronidase mRNA accumulated in response to androgen are controlled by alleles of Gus-r. Thus, Gus-r regulates the androgen responsiveness of glucuronidase synthesis by controlling the amount of glucuronidase mRNA available for translation and is a cis-acting genetic element that regulates the hormonal responsiveness of a specific mRNA.
D000483:Alleles; D000818:Animals; D003001:Cloning, Molecular; D004247:DNA / Q000378:metabolism; D005796:Genes / Q000187:drug effects*; D005966:Glucuronidase / Q000235:genetics*; D007668:Kidney / Q000201:enzymology*; D051379:Mice; D008815:Mice, Inbred Strains; D009693:Nucleic Acid Hybridization; D010957:Plasmids; D014176:Protein Biosynthesis; D012333:RNA, Messenger / Q000235:genetics*; D013739:Testosterone / Q000494:pharmacology*
D012333:RNA, Messenger; D013739:Testosterone; D004247:DNA; D005966:Glucuronidase