Two genetic elements regulate murine beta-glucuronidase synthesis following transcript accumulation

Abstract

Mutant alleles of two genetic regulatory elements, which underlie a three- to sixfold reduction in beta-glucuronidase (GUS) activity levels, distinguish mice of the H haplotype from those of the other two common GUS haplotypes, A and B. Both elements are tightly linked to the GUS structural gene over which they exert control. One (Gus-u) exerts a cis-active effect upon GUS activity levels in all tissues at all times while the other (Gus-t) regulates GUS activity in trans after the 12th postnatal day in certain tissues. While previous studies show that differences in the rate of GUS synthesis account for the combined effects of these two elements in liver of adult mice, we demonstrate the separate effects of each on GUS synthesis at times during early postnatal development when their individual expressions can be distinguished. Assessments of the relative levels of S1 nuclease protection of a radiolabeled GUS antisense RNA probe after hybridization with total liver RNA preparations from adult mice of A and H haplotypes reveal no differences. These results argue that Gus-u and Gus-t exert their control of GUS expression subsequent to the accumulation of processed GUS transcripts.