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

TitleRenin-1 is essential for normal renal juxtaglomerular cell granulation and macula densa morphology.
Publication TypeJournal Article
Year of Publication1997
AuthorsClark AF, Sharp MG, Morley SD, Fleming S, Peters J, Mullins JJ
JournalJ Biol Chem
Date Published1997 Jul 18
KeywordsAnimals, Blood Pressure, Cloning, Molecular, DNA Primers, Female, Homeostasis, Hypotension, Isoenzymes, Juxtaglomerular Apparatus, Kidney, Kidney Tubules, Distal, Male, Mice, Mice, Knockout, Polymerase Chain Reaction, Renin, Restriction Mapping, Sex Characteristics

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.

Alternate JournalJ. Biol. Chem.
PubMed ID9218454