Hypocalcemia and osteopathy in mice with kidney‐specific megalin gene defect

@article{Leheste2003HypocalcemiaAO,
  title={Hypocalcemia and osteopathy in mice with kidney‐specific megalin gene defect},
  author={J R Leheste and Flemming Melsen and Maren Wellner and Pernille Jansen and Uwe Schlichting and I. C. E. Renner-M{\"u}ller and Troels Torp Andreassen and E. Wolf and Sebastian Bachmann and Anders Nykjaer and Thomas E. Willnow},
  journal={The FASEB Journal},
  year={2003},
  volume={17}
}
Megalin is an endocytic receptor highly expressed in the proximal tubules of the kidney. Recently, we demonstrated that this receptor is essential for the renal uptake and conversion of 25‐OH vitamin D3 to 1,25‐(OH)2 vitamin D3, a central step in vitamin D and bone metabolism. Unfortunately, the perinatal lethality of the conventional megalin knockout mouse model precluded the detailed analysis of the significance of megalin for calcium homeostasis and bone turnover in vivo. Here, we have… 

Megalin and Vitamin D Metabolism—Implications in Non-Renal Tissues and Kidney Disease

An overview of the current knowledge of megalin function in the context of vitamin D metabolism is provided, with an emphasis on extrarenal megal in, an area that clearly requires further investigation.

Role of Megalin, a Proximal Tubular Endocytic Receptor, in Calcium and Phosphate Homeostasis

  • A. SaitoN. IinoT. TakedaF. Gejyo
  • Biology, Medicine
    Therapeutic apheresis and dialysis : official peer-reviewed journal of the International Society for Apheresis, the Japanese Society for Apheresis, the Japanese Society for Dialysis Therapy
  • 2007
Megalin is expressed at the apical membranes of proximal tubule cells, acting as an endocytic receptor for a variety of ligands filtered by glomeruli, and decreased expression of megalin may be associated with the pathogenesis of hyperphosphaturia observed in patients with Dent's disease.

Megalin-mediated reuptake of retinol in the kidneys of mice is essential for vitamin A homeostasis.

It is demonstrated that urinary ROH excretion caused by megalin deficiency requires accelerated mobilization of hepatic VA stores to maintain normal plasma ROH levels, which suggests that megal in plays an essential role in systemic VA homeostasis.

Diagnosis and Management of Renal Osteodystrophy in Children

“Renal osteodystrophy” is the specific term used to describe the bone pathology that occurs as a complication of CKD and is therefore one aspect of the CKD-MBD.

Kidney-specific upregulation of vitamin D3 target genes in ClC-5 KO mice.

Mutations in ClC-5 cause Dent's disease, a disorder associated with low molecular weight proteinuria, hyperphosphaturia, and kidney stones. ClC-5 is a Cl(-)/H(+)-exchanger predominantly expressed in

Dysregulation of the Intrarenal Vitamin D Endocytic Pathway in a Nephropathy-Prone Mouse Model of Type 1 Diabetes

The studies show that intrarenal vitamin D handling is altered in the diabetic kidney, and they suggest that in T1D, urinary losses of VDBP may portend risk for intra Renal and extrarenal Vitamin D deficiencies.

Mouse model of proximal tubule endocytic dysfunction.

  • K. WeyerTina Storm R. Nielsen
  • Biology, Medicine
    Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association
  • 2011
The viable megalin/cubilin double-deficient mice now allow for detailed large-scale group analysis, and it is anticipated that the mice will be of great value as an animal model for proximal tubulopathies with disrupted endocytosis.

Selective Ablation of Megalin in the Retinal Pigment Epithelium Results in Megaophthalmos, Macromelanosome Formation and Severe Retina Degeneration

Postnatal loss of megalin in the RPE induces dramatic and rapid ocular growth and retinal degeneration compatible with the high myopia observed in Donnai-Barrow patients.

Megalin contributes to the early injury of proximal tubule cells during nonselective proteinuria.

Results show that megalin plays a pivotal role in the re absorption of small to large molecular size proteins and provides direct in vivo evidence that reabsorption of filtered proteins triggers events leading to tubule injury.
...

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