Biomedical subjects

L T Bracey

Publications and source records attributed to L T Bracey.

3 recordsLinked to original sources

PubMed1989

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.

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PubMed1988

Androgen induction of beta-glucuronidase translational yield in submaxillary gland of B6.N mice.

Androgens induce the synthesis of murine beta-glucuronidase (GUS) 10-fold in the submaxillary gland of B6.PAC-Gusn mice without a concomitant increase in GUS mRNA levels. Since the rate of GUS synthesis per mRNA molecule, or translational yield, is a function of both the efficiency with which the message is translated and the fraction of newly made polypeptides that are incorporated into GUS tetramers, we conclude that androgen induces at least one of these components in the submaxillary gland of B6.N mice. Genetic variation in the submaxillary gland induction response was tested for using six congenic mice strains, each carrying a different haplotype of the Gus gene complex on a C57BL/6J genetic background. The results indicate that the DNA sequences determining androgen responsiveness of the Gus gene in the submaxillary gland are linked to the Gus gene complex and that the DNA sequences determining the submaxillary gland response are distinct from those determining the androgen induction of GUS mRNA in kidney.

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PubMed1987

Changes in translational yield regulate tissue-specific expression of beta-glucuronidase.

The number of beta-glucuronidase (GUS; beta-D-glucuronoside glucuronosohydrolase, EC 3.2.1.31) molecules per cell varies as much as 12-fold among mouse tissues. To identify the regulatory mechanisms responsible, estimates of the rates of GUS protein synthesis (ks) and degradation (kd) were obtained for six tissues in the B6.PAC-Gusn mouse strain, which carries the N haplotype of the GUS gene. Differences in enzyme levels among tissues were predominantly due to differences in rates of enzyme synthesis; only brain differed significantly in the rate of protein degradation. Typically, tissues contain about 2 molecules of GUS mRNA per cell. Differences in GUS mRNA levels were found among tissues, but these were not sufficient to account for observed differences in ks. This suggests that tissues differ in translational yield, which is defined as the product of the efficiency with which the GUS message is translated and the fraction of newly made polypeptides that are successfully matured into GUS tetramers. Experimental estimates of translational yield confirmed that this is indeed a source of tissue differences in GUS gene regulation. This finding also proved to be true of the B haplotype of the GUS gene. The differential regulation of special-function genes is, in general, effected transcriptionally. In contrast, the differential regulation of several "housekeeping" genes has been reported to arise from changes in mRNA maturation and/or stability. It is now apparent that translational yield, which is an aspect of protein synthesis, can also serve as a differential regulatory mechanism.

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