Evaluating a model of an NRE mediated tissue-specific expression of murine renin genes

• Published in: Hypertension (Dallas, Tex. 1979) Vol. 37; no. 1; pp. 105 - 109
• Main Authors: ABONIA, J. Pablo, HOWLES, Philip N, ABEL, Kenneth J, BLACK, Thomas A, JONES, Craig A, GROSS, Kenneth W
• Format: Journal Article
• Language: English
• Published: Philadelphia, PA Lippincott 2001; Hagerstown, MD American Heart Association, Inc
• Subjects: Arterial hypertension. Arterial hypotension; Biological and medical sciences; Blood and lymphatic vessels; Cardiology. Vascular system; Experimental diseases; Medical sciences; Hypertension; Enzyme; Rodentia; Cardiovascular disease; Gene expression; Genetic determinism; Variant; Peptidases; Vertebrata; Mammalia; Renin; Mouse; Animal; Hydrolases; Aspartic endopeptidases; Locus
• ISSN: 0194-911X; 1524-4563
• DOI: 10.1161/01.HYP.37.1.105

-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.