Alterations of renal phenotype and gene expression profiles due to protein overload in NOD-related mouse strains.

Hdl Handle:
http://hdl.handle.net/10675.2/23
Title:
Alterations of renal phenotype and gene expression profiles due to protein overload in NOD-related mouse strains.
Authors:
Wilson, Karen H S; McIndoe, Richard A; Eckenrode, Sarah E; Morel, Laurence; Agarwal, Anupam; Croker, Byron P; She, Jin-Xiong
Abstract:
BACKGROUND: Despite multiple causes, Chronic Kidney Disease is commonly associated with proteinuria. A previous study on Non Obese Diabetic mice (NOD), which spontaneously develop type 1 diabetes, described histological and gene expression changes incurred by diabetes in the kidney. Because proteinuria is coincident to diabetes, the effects of proteinuria are difficult to distinguish from those of other factors such as hyperglycemia. Proteinuria can nevertheless be induced in mice by peritoneal injection of Bovine Serum Albumin (BSA). To gain more information on the specific effects of proteinuria, this study addresses renal changes in diabetes resistant NOD-related mouse strains (NON and NOD.B10) that were made to develop proteinuria by BSA overload. METHODS: Proteinuria was induced by protein overload on NON and NOD.B10 mouse strains and histology and microarray technology were used to follow the kidney response. The effects of proteinuria were assessed and subsequently compared to changes that were observed in a prior study on NOD diabetic nephropathy. RESULTS: Overload treatment significantly modified the renal phenotype and out of 5760 clones screened, 21 and 7 kidney transcripts were respectively altered in the NON and NOD.B10. Upregulated transcripts encoded signal transduction genes, as well as markers for inflammation (Calmodulin kinase beta). Down-regulated transcripts included FKBP52 which was also down-regulated in diabetic NOD kidney. Comparison of transcripts altered by proteinuria to those altered by diabetes identified mannosidase 2 alpha 1 as being more specifically induced by proteinuria. CONCLUSION: By simulating a component of diabetes, and looking at the global response on mice resistant to the disease, by virtue of a small genetic difference, we were able to identify key factors in disease progression. This suggests the power of this approach in unraveling multifactorial disease processes.
Citation:
BMC Nephrol. 2005 Dec 21; 6:17
Issue Date:
19-Jan-2006
URI:
http://hdl.handle.net/10675.2/23
DOI:
10.1186/1471-2369-6-17
PubMed ID:
16371158
PubMed Central ID:
PMC1334202
Type:
Journal Article; Research Support, N.I.H., Extramural
ISSN:
1471-2369
Appears in Collections:
Center for Biotechnology and Genomic Medicine: Faculty Research and Publications

Full metadata record

DC FieldValue Language
dc.contributor.authorWilson, Karen H Sen_US
dc.contributor.authorMcIndoe, Richard Aen_US
dc.contributor.authorEckenrode, Sarah Een_US
dc.contributor.authorMorel, Laurenceen_US
dc.contributor.authorAgarwal, Anupamen_US
dc.contributor.authorCroker, Byron Pen_US
dc.contributor.authorShe, Jin-Xiongen_US
dc.date.accessioned2010-09-24T20:59:22Z-
dc.date.available2010-09-24T20:59:22Z-
dc.date.issued2006-01-19en_US
dc.identifier.citationBMC Nephrol. 2005 Dec 21; 6:17en_US
dc.identifier.issn1471-2369en_US
dc.identifier.pmid16371158en_US
dc.identifier.doi10.1186/1471-2369-6-17en_US
dc.identifier.urihttp://hdl.handle.net/10675.2/23-
dc.description.abstractBACKGROUND: Despite multiple causes, Chronic Kidney Disease is commonly associated with proteinuria. A previous study on Non Obese Diabetic mice (NOD), which spontaneously develop type 1 diabetes, described histological and gene expression changes incurred by diabetes in the kidney. Because proteinuria is coincident to diabetes, the effects of proteinuria are difficult to distinguish from those of other factors such as hyperglycemia. Proteinuria can nevertheless be induced in mice by peritoneal injection of Bovine Serum Albumin (BSA). To gain more information on the specific effects of proteinuria, this study addresses renal changes in diabetes resistant NOD-related mouse strains (NON and NOD.B10) that were made to develop proteinuria by BSA overload. METHODS: Proteinuria was induced by protein overload on NON and NOD.B10 mouse strains and histology and microarray technology were used to follow the kidney response. The effects of proteinuria were assessed and subsequently compared to changes that were observed in a prior study on NOD diabetic nephropathy. RESULTS: Overload treatment significantly modified the renal phenotype and out of 5760 clones screened, 21 and 7 kidney transcripts were respectively altered in the NON and NOD.B10. Upregulated transcripts encoded signal transduction genes, as well as markers for inflammation (Calmodulin kinase beta). Down-regulated transcripts included FKBP52 which was also down-regulated in diabetic NOD kidney. Comparison of transcripts altered by proteinuria to those altered by diabetes identified mannosidase 2 alpha 1 as being more specifically induced by proteinuria. CONCLUSION: By simulating a component of diabetes, and looking at the global response on mice resistant to the disease, by virtue of a small genetic difference, we were able to identify key factors in disease progression. This suggests the power of this approach in unraveling multifactorial disease processes.en_US
dc.rightsThe PMC Open Access Subset is a relatively small part of the total collection of articles in PMC. Articles in the PMC Open Access Subset are still protected by copyright, but are made available under a Creative Commons or similar license that generally allows more liberal redistribution and reuse than a traditional copyrighted work. Please refer to the license statement in each article for specific terms of use. The license terms are not identical for all articles in this subset.en_US
dc.subject.meshAnimalsen_US
dc.subject.meshDiabetes Mellitus / etiologyen_US
dc.subject.meshDiabetic Nephropathies / complicationsen_US
dc.subject.meshDisease Susceptibilityen_US
dc.subject.meshGene Expressionen_US
dc.subject.meshGene Expression Profilingen_US
dc.subject.meshKidney / metabolism / pathology / physiopathologyen_US
dc.subject.meshMiceen_US
dc.subject.meshMice, Inbred NODen_US
dc.subject.meshOligonucleotide Array Sequence Analysisen_US
dc.subject.meshPhenotypeen_US
dc.subject.meshProteinuria / etiology / pathology / physiopathologyen_US
dc.subject.meshSerum Albumin, Bovineen_US
dc.titleAlterations of renal phenotype and gene expression profiles due to protein overload in NOD-related mouse strains.en_US
dc.typeJournal Articleen_US
dc.typeResearch Support, N.I.H., Extramuralen_US
dc.identifier.pmcidPMC1334202en_US
dc.contributor.corporatenameCenter for Biotechnology and Genomic Medicineen_US

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