Electronic Resource
Mouse model for inherited renal fibrosis associated with endoplasmic reticulum stress
| العنوان: | Mouse model for inherited renal fibrosis associated with endoplasmic reticulum stress |
|---|---|
| المؤلفون: | UCL - SSS/IREC/NEFR - Pôle de Néphrologie, Piret, Sian E., Olinger, Eric, Reed, Anita A. C., Nesbit, M. Andrew, Hough, Tertius A., Bentley, Liz, Devuyst, Olivier, Cox, Roger, Thakker, Rajesh V. |
| المصدر: | Disease Models & Mechanisms, Vol. 10, no.6, p. 773-786 (2017) |
| بيانات النشر: | The Company of Biologists 2017 |
| نوع الوثيقة: | Electronic Resource |
| مستخلص: | Renal fibrosis is a common feature of renal failure resulting from multiple etiologies, including diabetic nephropathy, hypertension and inherited renal disorders. However, the mechanisms of renal fibrosis are incompletely understood and we therefore explored these by establishing a mouse model for a renal tubular disorder, referred to as autosomal dominant tubulointerstitial kidney disease (ADTKD) due to missense uromodulin (UMOD) mutations (ADTKD-UMOD). ADTKD-UMOD, which is associated with retention of mutant uromodulin in the endoplasmic reticulum (ER) of renal thick ascending limb cells, is characterized by hyperuricemia, interstitial fibrosis, inflammation and renal failure, and we used targeted homologous recombination to generate a knock-in mouse model with an ADTKD-causing missense cysteine to arginine uromodulin mutation (C125R). Heterozygous and homozygous mutant mice developed reduced uric acid excretion, renal fibrosis, immune cell infiltration and progressive renal failure, with decreased maturation and excretion of uromodulin, due to its retention in the ER. The ER stress marker 78 kDa glucose-regulated protein (GRP78) was elevated in cells expressing mutant uromodulin in heterozygous and homozygous mutant mice, and this was accompanied, both in vivo and ex vivo, by upregulation of two unfolded protein response pathways in primary thick ascending limb cells from homozygous mutant mice. However, this did not lead to an increase in apoptosis in vivo Thus, we have developed a novel mouse model for renal fibrosis, which will be a valuable resource to decipher the mechanisms linking uromodulin mutations with ER stress and renal fibrosis. |
| مصطلحات الفهرس: | General Biochemistry, Genetics and Molecular Biology, Immunology and Microbiology (miscellaneous), Medicine (miscellaneous), Neuroscience (miscellaneous), info:eu-repo/semantics/article |
| URL: | |
| الاتاحة: | Open access content. Open access content info:eu-repo/semantics/openAccess |
| ملاحظة: | English |
| Other Numbers: | UCDLC oai:dial.uclouvain.be:boreal:250835 boreal:250835 info:doi/10.1242/dmm.029488 urn:ISSN:1754-8403 urn:EISSN:1754-8411 1288277852 |
| المصدر المساهم: | UNIVERSITE CATHOLIQUE DE LOUVAIN From OAIster®, provided by the OCLC Cooperative. |
| رقم الانضمام: | edsoai.on1288277852 |
| قاعدة البيانات: | OAIster |
| الوصف غير متاح. |