Ablation of renin-expressing juxtaglomerular cells results in a distinct kidney phenotype

ES Pentz, MA Moyano, BA Thornhill… - American Journal …, 2004 - journals.physiology.org
ES Pentz, MA Moyano, BA Thornhill, MLS Sequeira Lopez, RA Gomez
American Journal of Physiology-Regulatory, Integrative and …, 2004journals.physiology.org
Renin-expressing cells are peculiar in that they act as differentiated cells, producing the
hormone renin, while they also seem to act as progenitors for other renal cell types. As such,
they may have functions independent of their ability to generate renin/angiotensin. To test
this hypothesis, we ablated renin-expressing cells during development by placing diphtheria
toxin A chain (DTA) under control of the Ren1d mouse renin promoter by homologous
recombination in a two-renin gene strain (Ren2 and Ren1d). Renin-expressing cells are …
Renin-expressing cells are peculiar in that they act as differentiated cells, producing the hormone renin, while they also seem to act as progenitors for other renal cell types. As such, they may have functions independent of their ability to generate renin/angiotensin. To test this hypothesis, we ablated renin-expressing cells during development by placing diphtheria toxin A chain (DTA) under control of the Ren1d mouse renin promoter by homologous recombination in a two-renin gene strain (Ren2 and Ren1d). Renin-expressing cells are essentially absent from kidneys in homozygotes (DTA/DTA) which, unlike wild-type mice, are unable to recruit renin-expressing cells when homeostasis is threatened. In contrast, renin staining in the submandibular gland (SMG), which expresses mainly Ren2, is normal. Homozygous mice survive normally, but the kidneys are small and have morphological abnormalities: 25% of the glomeruli are hyperplastic or atrophic, tubules are dilated and atrophic, and areas of undifferentiated cells exist near the atrophic glomeruli and tubules. However, in contrast to the very abnormal renal vessels found when renin-angiotensin system genes are deleted, the kidney vessels in homozygotes have normal wall thickness and no decrease in lumen size. Homozygotes have severely reduced kidney and plasma renin concentrations and females have reduced blood pressure. Homozygotes have elevated blood urea nitrogen and potassium levels, which are suggestive of altered renal function. We conclude that renin cells per se are necessary for the morphological integrity of the kidney and may have a role in maintenance of normal kidney function.
American Physiological Society