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

Karen H.S. Wilson, Richard A McIndoe, Sarah Eckenrode, Laurence Morel, Anupam Agarwal, Byron P. Croker, Jin-Xiong She

Research output: Contribution to journalArticle

6 Citations (Scopus)

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.

Original languageEnglish (US)
Article number17
JournalBMC Nephrology
Volume6
DOIs
StatePublished - Dec 21 2005

Fingerprint

Inbred NOD Mouse
Proteinuria
Transcriptome
Phenotype
Kidney
Proteins
Bovine Serum Albumin
Mannosidases
Calcium-Calmodulin-Dependent Protein Kinases
Diabetic Nephropathies
Type 1 Diabetes Mellitus
Chronic Renal Insufficiency
Hyperglycemia
Disease Progression
Signal Transduction
Histology
Clone Cells
Inflammation
Technology
Gene Expression

ASJC Scopus subject areas

  • Nephrology

Cite this

Alterations of renal phenotype and gene expression profiles due to protein overload in NOD-related mouse strains. / Wilson, Karen H.S.; McIndoe, Richard A; Eckenrode, Sarah; Morel, Laurence; Agarwal, Anupam; Croker, Byron P.; She, Jin-Xiong.

In: BMC Nephrology, Vol. 6, 17, 21.12.2005.

Research output: Contribution to journalArticle

Wilson, Karen H.S. ; McIndoe, Richard A ; Eckenrode, Sarah ; Morel, Laurence ; Agarwal, Anupam ; Croker, Byron P. ; She, Jin-Xiong. / Alterations of renal phenotype and gene expression profiles due to protein overload in NOD-related mouse strains. In: BMC Nephrology. 2005 ; Vol. 6.
@article{740bf7ae1ca04ca18f2a8e315e571511,
title = "Alterations of renal phenotype and gene expression profiles due to protein overload in NOD-related mouse strains",
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.",
author = "Wilson, {Karen H.S.} and McIndoe, {Richard A} and Sarah Eckenrode and Laurence Morel and Anupam Agarwal and Croker, {Byron P.} and Jin-Xiong She",
year = "2005",
month = "12",
day = "21",
doi = "10.1186/1471-2369-6-17",
language = "English (US)",
volume = "6",
journal = "BMC Nephrology",
issn = "1471-2369",
publisher = "BioMed Central",

}

TY - JOUR

T1 - Alterations of renal phenotype and gene expression profiles due to protein overload in NOD-related mouse strains

AU - Wilson, Karen H.S.

AU - McIndoe, Richard A

AU - Eckenrode, Sarah

AU - Morel, Laurence

AU - Agarwal, Anupam

AU - Croker, Byron P.

AU - She, Jin-Xiong

PY - 2005/12/21

Y1 - 2005/12/21

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=31144451231&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=31144451231&partnerID=8YFLogxK

U2 - 10.1186/1471-2369-6-17

DO - 10.1186/1471-2369-6-17

M3 - Article

C2 - 16371158

AN - SCOPUS:31144451231

VL - 6

JO - BMC Nephrology

JF - BMC Nephrology

SN - 1471-2369

M1 - 17

ER -