RGD Reference Report - A murine model of phosphate nephropathy. - Rat Genome Database

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A murine model of phosphate nephropathy.

Authors: Eller, P  Eller, K  Kirsch, AH  Patsch, JJ  Wolf, AM  Tagwerker, A  Stanzl, U  Kaindl, R  Kahlenberg, V  Mayer, G  Patsch, JR  Rosenkranz, AR 
Citation: Eller P, etal., Am J Pathol. 2011 May;178(5):1999-2006.
RGD ID: 6893463
Pubmed: (View Article at PubMed) PMID:21514417
DOI: Full-text: DOI:10.1016/j.ajpath.2011.01.024

We established a murine model of phosphate nephropathy with secondary hyperparathyroidism. db/db mice, which develop obesity and type 2 diabetes mellitus, were uninephrectomized at the age of 6 weeks and were fed either standard chow or a phosphorus-rich diet during the next 8 weeks. Thereafter, renal cryosections showed abundant tubular casts with a strong histochemical von Kossa reaction in all db/db mice on the phosphorus-rich diet but none in the controls. X-ray diffraction and Raman spectroscopy proved that these tubular casts consist mostly of hydroxyapatite Ca(5)(PO(4))(3)(OH). These intraluminal precipitations were located in distal tubuli and collecting ducts and were associated with degenerative tubular changes and peritubular infiltration of T cells and macrophages. In line, kidneys of db/db mice on the phosphorus-rich diet displayed significantly increased mRNA expression of the T(H)1 cytokines interferon gamma, IL-6, and tumor necrosis factor alpha. In addition, mice developed signs of secondary hyperparathyroidism as shown by elevated serum phosphate, decreased serum calcium, and increased parathyroid hormone, osteopontin, and fibroblast growth factor 23 levels. db/db mice on the phosphorus-rich diet also presented with significantly lower body weight, lower homeostasis model assessment of insulin resistance index, and hypertrophic cardiomyopathy. Thus, we provide a murine model of phosphate nephropathy and secondary hyperparathyroidism, which can be used for future pharmacologic and pathophysiologic studies to analyze the effect of hyperphosphatemia on renal, metabolic, and cardiovascular phenotypes.

Annotation

Disease Annotations    
Kidney Calculi  (IEP,ISO)

Objects Annotated

Genes (Rattus norvegicus)
Ifng  (interferon gamma)

Genes (Mus musculus)
Ifng  (interferon gamma)

Genes (Homo sapiens)
IFNG  (interferon gamma)


Additional Information