A novel model of adenine-induced tubulointerstitial nephropathy in mice
| Autor: | Ting Jia, Göran Andersson, Bengt Lindholm, Karin Edvardsson, Annika Wernerson, Tobias E. Larsson, Yves Sabbagh, Risul Amin, Susan C. Schiavi, Hannes Olauson, Karolina Lindberg |
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| Jazyk: | angličtina |
| Rok vydání: | 2013 |
| Předmět: |
Nephrology
medicine.medical_specialty Pathology Mineral metabolism Experimental renal failure Bone resorption Muscle hypertrophy Mice Fibrosis FGF23 Internal medicine Chronic kidney disease medicine CKD CKD-MBD Animals FGF-23 business.industry Adenine medicine.disease Uremia Mice Inbred C57BL Disease Models Animal Fibroblast Growth Factor-23 medicine.anatomical_structure Technical Advance Nephritis Interstitial Secondary hyperparathyroidism Bone marrow business Kidney disease |
| Zdroj: | BMC Nephrology |
| ISSN: | 1471-2369 |
| Popis: | Background In vivo models of uremia are important tools to study numerous aspects of acute and chronic kidney disease. Mouse models are pivotal because most genetically engineered animal models are mice, which allow dissecting the impact of selected target genes in renal failure. Adenine-based protocols to induce renal failure are available in rats, but have not been adapted in mice due to their reluctance to consume adenine. In the current paper we developed a novel method for induction of renal failure through dietary delivery of adenine mixed in a casein-based diet. Results After an induction phase, a stable model of renal impairment was obtained (target urea range 80–100 mg/dL), mimicking several aspects of chronic kidney disease - mineral and bone disorder including secondary hyperparathyroidism, bone abnormalities and pathological elevation of FGF23. No deaths occurred and the level of uremia was adaptable through adjustments of the adenine content, providing significant advantages compared to existing models. In an 8-week proof-of-concept study, renal histology showed mainly a tubulointerstitial damage with infiltrating leukocytes, interstitial edema and widening of the Bownman's space. Fibrosis was present in most animals as defined by histology and gene expression changes of fibrosis markers. Parathyroid cell proliferation was markedly increased but without signs of glandular hypertrophy. Skeletal histology showed increased trabecular bone and bone marrow adiposity whereas bone biomarkers (CTX and PINP) suggested higher bone formation, but surprisingly, lower bone resorption and perturbations in mineral metabolism. Conclusions We present a novel, non-surgical method for induction of renal failure in mice. This is an important complement to existing uremic models for pathophysiological studies in acute and chronic kidney disease, especially in terms of tubulointerstitial lesions. |
| Databáze: | OpenAIRE |
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