| Autor: |
Schnoz C; Institute of Anatomy, University of Zurich, Winterthurerstrasse 190, CH-8057, Zurich, Switzerland., Moser S; Institute of Anatomy, University of Zurich, Winterthurerstrasse 190, CH-8057, Zurich, Switzerland., Kratschmar DV; Division of Molecular and Systems Toxicology, Department of Pharmaceutical Sciences, University of Basel, Basel, Switzerland., Odermatt A; Division of Molecular and Systems Toxicology, Department of Pharmaceutical Sciences, University of Basel, Basel, Switzerland.; National Centre of Competence in Research 'Kidney.CH', University of Zurich, 8057, Zurich, Switzerland., Loffing-Cueni D; Institute of Anatomy, University of Zurich, Winterthurerstrasse 190, CH-8057, Zurich, Switzerland., Loffing J; Institute of Anatomy, University of Zurich, Winterthurerstrasse 190, CH-8057, Zurich, Switzerland. johannes.loffing@anatomy.uzh.ch.; National Centre of Competence in Research 'Kidney.CH', University of Zurich, 8057, Zurich, Switzerland. johannes.loffing@anatomy.uzh.ch. |
| Abstrakt: |
The renal distal convoluted tubule (DCT) is critical for the fine-tuning of urinary ion excretion and the control of blood pressure. Ion transport along the DCT is tightly controlled by posttranscriptional mechanisms including a complex interplay of kinases, phosphatases, and ubiquitin ligases. Previous work identified the transcription factor Prox-1 as a gene significantly enriched in the DCT of adult mice. To test if Prox-1 contributes to the transcriptional regulation of DCT function and structure, we developed a novel mouse model (NCC cre :Prox-1 flox/flox ) for an inducible deletion of Prox-1 specifically in the DCT. The deletion of Prox-1 had no obvious impact on DCT structure and growth independent whether the deletion was achieved in newborn or adult mice. Furthermore, DCT-specific Prox-1 deficiency did not alter DCT-proliferation in response to loop diuretic treatment. Likewise, the DCT-specific deletion of Prox-1 did not cause other gross phenotypic abnormalities. Body weight, urinary volume, Na + and K + excretion as well as plasma Na + , K + , and aldosterone levels were similar in Prox-1 DCT KO and Prox-1 DCT Ctrl mice. However, Prox-1 DCT KO mice exhibited a significant hypomagnesemia with a profound downregulation of the DCT-specific apical Mg 2+ channel TRPM6 and the NaCl cotransporter (NCC) at both mRNA and protein levels. The expression of other proteins involved in distal tubule Mg 2+ and Na + handling was not affected. Thus, Prox-1 is a DCT-enriched transcription factor that does not control DCT growth but contributes to the molecular control of DCT-dependent Mg 2+ homeostasis in the adult kidney. |
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