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

We have used comparative sequence analysis to evaluate a putative silencer element that has been proposed to be involved in the differential tissue-ex pression of the murine renin genes: Ren-1 and Ren-2. In the mouse, these ge nes share a similar pattern of tissue-specific renin expression. One signif icant difference is seen in the submandibular gland (SMG) where renin expre ssion 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 f rom the interplay among a negative regulatory element and a cAMP responsive dement, their respective binding factors, and the disruption of the negati ve regulatory element by an insertion (M2) that is found in Ren-2 but not i n 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 close ly related mouse species M. hortulanus, This species shares the same high l evel of Ren-2 expression in the SMG as seen in other Ren-a positive mouse s trains. However, the Ren-2 M, hortulanus allele does not appear to contain the disruptive M2 element according to restriction-enzyme mapping. Our sequ ence analysis confirms that the M. hortulanus Ren-2 allele contains the sam e sequence elements present in the DBA/2 Ren-2 allele except for the M2 ele ment. Moreover, the proposed negative regulatory element is intact at the s equence level in Ren-2 M. hortulanus allele. This analysis suggests that an y involvement of the negative regulatory element in differential Ren-l and Ren-a expression in the SMG is not as straightforward as previously hypothe sized.