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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Center for Biotechnology and Genomic Medicine, Medical College of Georgia, PV6B108, Augusta, GA 30912-2400, USA. Karen.wilson@kmf.gu.se
authors.forename: Karen H S
authors.initials: KH
authors.lastname: Wilson
authors.forename: Richard A
authors.initials: RA
authors.lastname: McIndoe
authors.forename: Sarah
authors.initials: S
authors.lastname: Eckenrode
authors.forename: Laurence
authors.initials: L
authors.lastname: Morel
authors.forename: Anupam
authors.initials: A
authors.lastname: Agarwal
authors.forename: Byron P
authors.initials: BP
authors.lastname: Croker
authors.forename: Jin-Xiong
authors.initials: JX
authors.lastname: She
mesh_terms: D000818:Animals; D003920:Diabetes Mellitus / Q000209:etiology; D003928:Diabetic Nephropathies / Q000150:complications; D004198:Disease Susceptibility; D015870:Gene Expression; D020869:Gene Expression Profiling; D007668:Kidney / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D051379:Mice; D016688:Mice, Inbred NOD; D020411:Oligonucleotide Array Sequence Analysis; D010641:Phenotype; D011507:Proteinuria / Q000209:etiology / Q000473:pathology / Q000503:physiopathology*; D012710:Serum Albumin, Bovine
chemical_list: D012710:Serum Albumin, Bovine