肾病综合征
局灶节段性肾小球硬化
低蛋白血症
生物
微生物群
足细胞
失调
免疫学
病理
肾脏疾病
膜性肾病
肾小球肾炎
肾
医学
蛋白尿
内科学
肠道菌群
生物信息学
内分泌学
作者
Jasmin I. Maier,Manuel Rogg,Martin Helmstädter,Alena Sammarco,Gerd Walz,Martin Werner,Christoph Schell
出处
期刊:Cells
[Multidisciplinary Digital Publishing Institute]
日期:2021-06-15
卷期号:10 (6): 1509-1509
被引量:13
标识
DOI:10.3390/cells10061509
摘要
Glomerular kidney disease causing nephrotic syndrome is a complex systemic disorder and is associated with significant morbidity in affected patient populations. Despite its clinical relevance, well-established models are largely missing to further elucidate the implications of uncontrolled urinary protein loss. To overcome this limitation, we generated a novel, inducible, podocyte-specific transgenic mouse model (Epb41l5fl/fl*Nphs1-rtTA-3G*tetOCre), developing nephrotic syndrome in adult mice. Animals were comprehensively characterized, including microbiome analysis and multiplexed immunofluorescence imaging. Induced knockout mice developed a phenotype consistent with focal segmental glomerular sclerosis (FSGS). Although these mice showed hallmark features of severe nephrotic syndrome (including proteinuria, hypoalbuminemia and dyslipidemia), they did not exhibit overt chronic kidney disease (CKD) phenotypes. Analysis of the gut microbiome demonstrated distinct dysbiosis and highly significant enrichment of the Alistipes genus. Moreover, Epb41l5-deficient mice developed marked organ pathologies, including extramedullary hematopoiesis of the spleen. Multiplex immunofluorescence imaging demonstrated red pulp macrophage proliferation and mTOR activation as driving factors of hematopoietic niche expansion. Thus, this novel mouse model for adult-onset nephrotic syndrome reveals the significant impact of proteinuria on extra-renal manifestations, demonstrating the versatility of this model for nephrotic syndrome-related research.
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