The N haplotype of the murine beta-glucuronidase gene is altered in both its systemic regulation and its response to androgen induction.
A new haplotype of the beta-glucuronidase gene complex, [Gus]N, has been characterized following its transfer from the PAC/Cr strain to the standard strain C57BL/6J. The N haplotype contains a novel structural gene allele which encodes an allozyme differing from all previously characterized allozymes in both size and charge. Altered systemic regulation is exhibited by the [Gus]N haplotype. Multiple tissues contain levels of GUS protein that are 60 +/- 15% those found in the standard B haplotype. The regulatory mechanism for reduction is complex, involving tissue-specific changes in both enzyme synthesis and enzyme turnover. The changes in GUS protein synthesis do not result from changes in GUS mRNA levels. Instead, the amount of mature enzyme formed per mRNA molecule, or translational yield, is altered. These regulatory changes parallel those seen in other systemic regulatory variants of GUS which are also altered in translational yield. A commonality of mechanism among systemic regulatory variants of this gene is suggested. The N haplotype is also exceptional in the nature of its response to androgenic induction in kidney proximal tubule epithelial cells. The time course for GUS induction consists of a lag period followed by a progressive increase in mRNA, rate of enzyme synthesis, and enzyme activity. For the [Gus]N haplotype the lag is of an exceptionally short duration and the plateau is of a greater magnitude than for any haplotype previously described.
Bracey
L T
LT
Department of Genetics, University of California, Berkeley 94720.
Paigen
K
K
D000818:Animals; D004790:Enzyme Induction; D005786:Gene Expression Regulation / Q000187:drug effects; D005796:Genes; D005966:Glucuronidase / Q000096:biosynthesis / Q000235:genetics* / Q000302:isolation & purification; D006239:Haplotypes; D008099:Liver / Q000187:drug effects / Q000201:enzymology; D051379:Mice; D008810:Mice, Inbred C57BL; D008815:Mice, Inbred Strains; D009928:Organ Specificity; D012333:RNA, Messenger / Q000235:genetics; D013045:Species Specificity; D013739:Testosterone / Q000494:pharmacology*; D014158:Transcription, Genetic
D012333:RNA, Messenger; D013739:Testosterone; D005966:Glucuronidase