Renin-1 is essential for normal renal juxtaglomerular cell granulation and macula densa morphology

Allan F. Clark, Matthew G. F. Sharp, Steven D. Morley, Stewart Fleming, Jorg Peters, John J. Mullins

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    78 Citations (Scopus)

    Abstract

    The secretion of renin from granules stored in renal juxtaglomerular cells plays a key role in blood pressure homeostasis. The synthesis and release of renin and the extent of granulation is regulated by several mechanisms including signaling from the macula densa, neuronal input, and blood pressure. Through the use of a gene-targeting vector containing homology arms generated using the polymerase chain reaction, we have inactivated the Ren-1(d) gene, one of two mouse genes encoding renin, and report that lack of renin-1(d) results in altered morphology of the macula densa of the kidney distal tubule and complete absence of juxtaglomerular cell granulation. Furthermore, Ren-1(d-/-) mice exhibit sexually dimorphic hypotension. The altered growth morphology of the macula densa in Ren-1(d)-null mice should provide a tool for the investigation of the JG cell-macula densa signaling. Furthermore, the current data indicate that expression of the Ren-1(d) gene is a prerequisite for the formation of storage granules, even though the related protein renin-2 is present in these mice, suggesting that renin-1(d) and renin-2 are secreted by distinct pathways in vivo.
    Original languageEnglish
    Pages (from-to)18185-18190
    Number of pages6
    JournalJournal of Biological Chemistry
    Volume272
    Issue number29
    DOIs
    Publication statusPublished - 18 Jul 1997

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