title: Evaluating a Model of an NRE Mediated Tissue-Specific Expression of Murine Renin Genes.
abstract: -We have used comparative sequence analysis to evaluate a putative silencer element that has been proposed to be involved in the differential tissue-expression of the murine renin genes: Ren-1 and Ren-2. In the mouse, these genes share a similar pattern of tissue-specific renin expression. One significant difference is seen in the submandibular gland (SMG) where renin expression from the Ren-2 locus is 100-fold greater than the expression from the Ren-1 locus. One model proposes that this differential expression arises from the interplay among a negative regulatory element and a cAMP responsive element, their respective binding factors, and the disruption of the negative regulatory element by an insertion (M2) that is found in Ren-2 but not in Ren-1. The abrogation of the negative regulatory element's function as a result of the M2 insertion was proposed to be specifically responsible for the higher level of Ren-2 expression in the SMG as compared with Ren-1. We have assessed this hypothesis by looking at an allelic variant in the closely related mouse species M. hortulanus. This species shares the same high level of Ren-2 expression in the SMG as seen in other Ren-2 positive mouse strains. However, the Ren-2 M. hortulanus allele does not appear to contain the disruptive M2 element according to restriction-enzyme mapping. Our sequence analysis confirms that the M. hortulanus Ren-2 allele contains the same sequence elements present in the DBA/2 Ren-2 allele except for the M2 element. Moreover, the proposed negative regulatory element is intact at the sequence level in Ren-2 M. hortulanus allele. This analysis suggests that any involvement of the negative regulatory element in differential Ren-1 and Ren-2 expression in the SMG is not as straightforward as previously hypothesized.
authors.affiliation: Department of Molecular and Cellular Biology, Roswell Park Cancer Institute (J.P.A., T.A.B., C.A.J., K.W.G.), Buffalo, NY.
authors.forename: J. Pablo
authors.initials: JP
authors.lastname: Abonia
authors.forename: Philip N.
authors.initials: PN
authors.lastname: Howles
authors.forename: Kenneth J.
authors.initials: KJ
authors.lastname: Abel
authors.forename: Thomas A.
authors.initials: TA
authors.lastname: Black
authors.forename: Craig A.
authors.initials: CA
authors.lastname: Jones
authors.forename: Kenneth W.
authors.initials: KW
authors.lastname: Gross