Skip to main content
NCBI home page
Genetics logoLink to Genetics
. 1988 May;119(1):151–156. doi: 10.1093/genetics/119.1.151

Androgen Regulation of Murine β-Glucuronidase Expression: Identification and Characterization of a Nonresponse Variant

S D Lund 1, D Miller 1, V Chapman 1, R E Ganschow 1
PMCID: PMC1203334  PMID: 3396859

Abstract

One of the major features of β-glucuronidase (GUS) expression in inbred strains of the house mouse, Mus musculus, is the responsiveness of this enzyme to androgen stimulation in tubule cells of the kidney. Both GUS-specific and nonspecific mutations have been described which define genes that serve to control this response. During examination of the expression of GUS in the interbreeding subspecies, Mus hortulanus, a new GUS haplotype was uncovered that is characterized, in part, by a lack of GUS response to androgen stimulation in an apparently responsive kidney. Blot hybridization analyses of kidney RNA with a radiolabeled murine GUS cDNA shows this lack of response to be reflected in GUS mRNA levels. The difference in heat stability of GUS activity between M. hortulanus and a responsive inbred strain, ICR/Ha, was utilized to assess the contribution of each parent to kidney levels of GUS in androgen-treated and -untreated F(1) progeny of these strains. The results, together with preliminary genetic studies, suggest that the element controlling this responsiveness (or the lack thereof) is cis-active and tightly linked to the GUS structural gene on chromosome 5. It is not known whether this element is identical to another GUS-specific, cis-active element, Gus-r, which also controls the androgen response of GUS in mouse kidney.

Full Text

The Full Text of this article is available as a PDF (1.6 MB).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Bailly A., Le Page C., Rauch M., Milgrom E. Sequence-specific DNA binding of the progesterone receptor to the uteroglobin gene: effects of hormone, antihormone and receptor phosphorylation. EMBO J. 1986 Dec 1;5(12):3235–3241. doi: 10.1002/j.1460-2075.1986.tb04634.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Bardin C. W., Bullock L. P., Sherins R. J., Mowszowicz I., Blackburn W. R. Androgen metabolism and mechanism of action in male pseudohermaphroditism: a study of testicular feminization. Recent Prog Horm Res. 1973;29:65–109. doi: 10.1016/b978-0-12-571129-6.50006-3. [DOI] [PubMed] [Google Scholar]
  3. Berger F. G., Loose D., Meisner H., Watson G. Androgen induction of messenger RNA concentrations in mouse kidney is posttranscriptional. Biochemistry. 1986 Mar 11;25(5):1170–1175. doi: 10.1021/bi00353a034. [DOI] [PubMed] [Google Scholar]
  4. Chirgwin J. M., Przybyla A. E., MacDonald R. J., Rutter W. J. Isolation of biologically active ribonucleic acid from sources enriched in ribonuclease. Biochemistry. 1979 Nov 27;18(24):5294–5299. doi: 10.1021/bi00591a005. [DOI] [PubMed] [Google Scholar]
  5. Dean D. C., Knoll B. J., Riser M. E., O'Malley B. W. A 5'-flanking sequence essential for progesterone regulation of an ovalbumin fusion gene. Nature. 1983 Oct 6;305(5934):551–554. doi: 10.1038/305551a0. [DOI] [PubMed] [Google Scholar]
  6. Feinberg A. P., Vogelstein B. A technique for radiolabeling DNA restriction endonuclease fragments to high specific activity. Anal Biochem. 1983 Jul 1;132(1):6–13. doi: 10.1016/0003-2697(83)90418-9. [DOI] [PubMed] [Google Scholar]
  7. Ganschow R., Paigen K. Glucuronidase phenotypes of inbred mouse strains. Genetics. 1968 Jul;59(3):335–349. doi: 10.1093/genetics/59.3.335. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Karin M., Haslinger A., Holtgreve H., Cathala G., Slater E., Baxter J. D. Activation of a heterologous promoter in response to dexamethasone and cadmium by metallothionein gene 5'-flanking DNA. Cell. 1984 Feb;36(2):371–379. doi: 10.1016/0092-8674(84)90230-7. [DOI] [PubMed] [Google Scholar]
  9. Karin M., Haslinger A., Holtgreve H., Richards R. I., Krauter P., Westphal H. M., Beato M. Characterization of DNA sequences through which cadmium and glucocorticoid hormones induce human metallothionein-IIA gene. Nature. 1984 Apr 5;308(5959):513–519. doi: 10.1038/308513a0. [DOI] [PubMed] [Google Scholar]
  10. Lusis A. J., Tomino S., Paigen K. Isolation, characterization, and radioimmunoassay of murine egasyn, a protein stabilizing glucuronidase membrane binding. J Biol Chem. 1976 Dec 25;251(24):7753–7760. [PubMed] [Google Scholar]
  11. Maurer R. A. Selective binding of the estradiol receptor to a region at least one kilobase upstream from the rat prolactin gene. DNA. 1985 Feb;4(1):1–9. doi: 10.1089/dna.1985.4.1. [DOI] [PubMed] [Google Scholar]
  12. Meredith S. A., Ganschow R. E. Apparent trans control of murine beta-glucuronidase synthesis by a temporal genetic element. Genetics. 1978 Dec;90(4):725–734. doi: 10.1093/genetics/90.4.725. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Mulvihill E. R., LePennec J. P., Chambon P. Chicken oviduct progesterone receptor: location of specific regions of high-affinity binding in cloned DNA fragments of hormone-responsive genes. Cell. 1982 Mar;28(3):621–632. doi: 10.1016/0092-8674(82)90217-3. [DOI] [PubMed] [Google Scholar]
  14. Ono S., Stenius C., Christian L., Harris C., Ivey C. More about the testosterone induction of kidney alcohol dehydrogenase activity in the mouse. Biochem Genet. 1970 Oct;4(5):565–577. doi: 10.1007/BF00486095. [DOI] [PubMed] [Google Scholar]
  15. PAIGEN K. The effect of mutation on the intracellular location of beta-glucuronidase. Exp Cell Res. 1961 Nov;25:286–301. doi: 10.1016/0014-4827(61)90280-4. [DOI] [PubMed] [Google Scholar]
  16. Paigen K. Acid hydrolases as models of genetic control. Annu Rev Genet. 1979;13:417–466. doi: 10.1146/annurev.ge.13.120179.002221. [DOI] [PubMed] [Google Scholar]
  17. Paigen K., Labarca C., Watson G. A regulatory locus for mouse beta-glucuronidase induction, Gur, controls messenger RNA activity. Science. 1979 Feb 9;203(4380):554–556. doi: 10.1126/science.760204. [DOI] [PubMed] [Google Scholar]
  18. Payvar F., DeFranco D., Firestone G. L., Edgar B., Wrange O., Okret S., Gustafsson J. A., Yamamoto K. R. Sequence-specific binding of glucocorticoid receptor to MTV DNA at sites within and upstream of the transcribed region. Cell. 1983 Dec;35(2 Pt 1):381–392. doi: 10.1016/0092-8674(83)90171-x. [DOI] [PubMed] [Google Scholar]
  19. Pfister K., Chapman V., Watson G., Paigen K. Genetic variation for enzyme structure and systemic regulation in two new haplotypes of the beta-glucuronidase gene of Mus musculus castaneus. J Biol Chem. 1985 Sep 25;260(21):11588–11594. [PubMed] [Google Scholar]
  20. Scheidereit C., Geisse S., Westphal H. M., Beato M. The glucocorticoid receptor binds to defined nucleotide sequences near the promoter of mouse mammary tumour virus. Nature. 1983 Aug 25;304(5928):749–752. doi: 10.1038/304749a0. [DOI] [PubMed] [Google Scholar]
  21. Schwarzlose W., Heim F. Effect of testosterone on glutamate-pyruvate-transaminase, glutamate-oxaloacetate-transaminase and glutamate-dehydrogenase in mice kidneys. Life Sci II. 1973 Feb 8;12(3):107–115. doi: 10.1016/0024-3205(73)90327-5. [DOI] [PubMed] [Google Scholar]
  22. Suske G., Wenz M., Cato A. C., Beato M. The uteroglobin gene region: hormonal regulation, repetitive elements and complete nucleotide sequence of the gene. Nucleic Acids Res. 1983 Apr 25;11(8):2257–2271. doi: 10.1093/nar/11.8.2257. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Swank R. T., Paigen K., Davey R., Chapman V., Labarca C., Watson G., Ganschow R., Brandt E. J., Novak E. Genetic regulation of mammalian glucuronidase. Recent Prog Horm Res. 1978;34:401–436. doi: 10.1016/b978-0-12-571134-0.50015-6. [DOI] [PubMed] [Google Scholar]
  24. Williams L., McDonald C., Higgins S. Sequence organisation of rat seminal vesicle F gene: location of transcriptional start point and sequence comparison with six other androgen-regulated genes. Nucleic Acids Res. 1985 Feb 11;13(3):659–672. doi: 10.1093/nar/13.3.659. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from Genetics are provided here courtesy of Oxford University Press

RESOURCES