A novel transgenic mouse model highlights molecular disruptions involved in the pathogenesis of Dent disease 1.

Dent disease (DD) is a hereditary renal disorder characterized by low molecular weight (LMW) proteinuria and progressive renal failure. Inactivating mutations of the CLCN5 gene encoding the 2Cl/Hexchanger ClC-5 have been identified in patients with DD type 1. ClC-5 is essentially expressed in proximal tubules (PT) where it is thought to play a role in maintaining an efficient endocytosis of LMW proteins.

Multiomics reveals multilevel control of renal and systemic metabolism by the renal tubular circadian clock.

Circadian rhythmicity in renal function suggests rhythmic adaptations in renal metabolism. To decipher the role of the circadian clock in renal metabolism, we studied diurnal changes in renal metabolic pathways using integrated transcriptomic, proteomic, and metabolomic analysis performed on control mice and mice with an inducible deletion of the circadian clock regulator Bmal1 in the renal tubule (cKOt). With this unique resource, we demonstrated that approximately 30% of RNAs, approximately 20% of proteins, and approximately 20% of metabolites are rhythmic in the kidneys of control mice.

Renal FGF23 signaling depends on redox protein Memo1 and promotes orthovanadate-sensitive protein phosphotyrosyl phosphatase activity.

Memo1 deletion in mice causes premature aging and an unbalanced metabolism partially resembling Fgf23 and Klotho loss-of-function animals. We report a role for Memo's redox function in renal FGF23-Klotho signaling using mice with postnatally induced Memo deficiency in the whole body (cKO). Memo cKO mice showed impaired FGF23-driven renal ERK phosphorylation and transcriptional responses.

Loss of Ecrg4 improves calcium oxalate nephropathy.

Kidney stone is one of the most frequent urinary tract diseases, affecting 10% of the population and displaying a high recurrence rate. Kidney stones are the result of salt supersaturation, including calcium and oxalate. We have previously identified Esophageal cancer-related gene 4 (Ecrg4) as being modulated by hypercalciuria.

Redox-Dependent Bone Alkaline Phosphatase Dysfunction Drives Part of the Complex Bone Phenotype in Mice Deficient for .

Mediator of ErbB2-driven cell Motility 1 (MEMO1) is an intracellular redox protein that integrates growth factors signaling with the intracellular redox state. We have previously reported that mice lacking displayed higher plasma calcium levels and other alterations of mineral metabolism, but the underlying mechanism was unresolved and the bone phenotype was not described. Here, we show that Cre/lox-mediated MEMO1 deletion in the whole body of C57Bl/6 mice (Memo cKO) leads to severely altered trabecular bone and lower mineralization, with preserved osteoblast and osteoclast number and activity, but altered osteoblast response to epidermal growth factor (EGF) and FGF2.