Allelic Expression of the Mouse Ren-1 Genes in the Anterior Prostate (Coagulating Gland)

Abstract

Renin is an aspartyl protease involved in blood pressure homeostasis and electrolyte balance. Inbred strains of mice have either one of two alleles fixed at the Rell-l locus on chromosome 1, Ren-1 ^c or Ren-1 ^d. Ren-1 ^d is found in association with a tightly linked duplicated locus, Ren-2. While RNA derived from both Ren-1 alleles and Ren-2 are detected at equivalent levels in the kidney, locus- and allele-specific expression differences are observed in several extra-renal tissues.

The anterior prostate (coagulating gland) in mice shows dramatic differences in the expression of the highly similar Ren-1 alleles. The anterior prostate is an abundant source of renin RNA in mice carrying the Ren-lc allele, while strains that harbor Ren-1 ^d (and Ren-2) do not accumulate detectable levels of renin RNA in this tissue. The results of genetic analyses, in which the respective Ren-1 alleles were present on alternative genetic backgrounds, indicate that the Ren-1 expression patterns observed in the anterior prostate are most likely regulated by closely associated sequences in cis. In situ hybridization analysis, using a renin cRNA probe, demonstrates that the accumulation of Ren-1 ^c RNA is restricted to the epithelial cells of the anterior prostate. SI nuclease analysis of anterior prostate RNA populations reveals that transcription initiates at the major transcription start site utilized in the kidney and other renin expressing tissues. In addition, a series of upstream initiation sites were also observed, several of which map within a 0.5 kb transposable-like element located 5’ of the mouse renin genes. Interestingly, the upstream start sites used in anterior prostate Ren-1 ^c transcription are similar to a series of start sites previously mapped in submandibular gland (SMG) derived Ren-1 ^c and Ren-2 RNA.

At present we are producing transgenic mice with chimeric constructs containing Ren-1 ^c flanking sequences linked to the reporter gene, SV40 T-antigen. Examination of T-antigen expression in these mice should help to localize cis-acting regions which regulate Ren-1 ^c expression in the anterior prostate. Furthermore, since T-antigen is capable of transforming many different cell types, renin directed T-antigen expression may lead to tumor formation and thus may provide an animal model for tumorigenesis in the anterior prostate region.