RGD Reference Report - Proteinuria and glomerulosclerosis in the Sabra genetic rat model of salt susceptibility. - Rat Genome Database

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Proteinuria and glomerulosclerosis in the Sabra genetic rat model of salt susceptibility.

Authors: Yagil, C  Sapojnikov, M  Katni, G  Ilan, Z  Zangen, SW  Rosenmann, E  Yagil, Y 
Citation: Yagil C, etal., Physiol Genomics 2002;9(3):167-78.
RGD ID: 629619
Pubmed: PMID:12045297   (View Abstract at PubMed)
DOI: DOI:10.1152/physiolgenomics.00014.2002   (Journal Full-text)

In search of an experimental model that would simulate the association between proteinuria and salt sensitivity in humans, we studied protein excretion in the Sabra rat model of salt susceptibility. Monthly measurements of urinary protein excretion in animals fed standard rat chow revealed that normotensive salt-sensitive SBH/y developed proteinuria that averaged 65 +/- 7 mg/day (n = 10) at 9 mo, whereas proteinuria in normotensive salt-resistant SBN/y was 39 +/- 4 mg/day (n = 10) (P < 0.01). Histopathological evaluation revealed focal and segmental glomerulosclerosis (FSGS) lesions grade 2 in SBH/y and normal histology in SBN/y. To amplify the differences between the strains, uninephrectomy was performed. At 9 mo, proteinuria in SBH/y with one kidney (SBH/y-1K) was 195 +/- 12 mg/day (n = 10) and in SBN/y was 128 +/- 10 mg/day (n = 10) (P < 0.001); histopathology revealed FSGS grade 3 in SBH/y-1K and grade 1-2 in SBN/y-1K. To determine the effect of salt loading, animals were provided with 8% NaCl in chow, causing hypertension in SBH/y but not in SBN/y. Proteinuria markedly increased in both SBH/y with two kidneys (SBH/y-2K) and SBH/y-1K, but not in SBN/y; histopathology revealed FSGS grade 1-2 in SBH/y-2K, grade 2 in SBH/y-1K, no lesions in SBN/y-2K, and grade 0-1 in SBN/y-1K. We concluded that the SBH/y strain is more susceptible to develop proteinuria and glomerulosclerosis than SBN/y. In search for the genetic basis of this phenomenon, we investigated the role of candidate proteinuric gene loci. Consomic strains were constructed by introgressing chromosome 1 (which harbors the rf-1 and rf-2 proteinuric loci) or chromosome 17 (which harbors rf-5) from SBH/y onto the SBN/y genomic background. The resulting consomic strains developed marked proteinuria that was severalfold higher than in SBN/y-1K; histopathological evaluation, however, revealed FSGS lesions grade 1-2, similar to those found in SBN/y-1K and less severe than in SBH/y-1K. These results suggest a functional role of gene systems located on chromosomes 1 and 17 in inducing proteinuria in the salt-susceptible Sabra rat strain. These genetic loci do not appear to harbor major genes for glomerulosclerosis.



RGD Manual Disease Annotations    Click to see Annotation Detail View

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
SBH/YglRatfocal segmental glomerulosclerosis severityIAGPunilateral nephrectomycompared to uninephrectomized SBN/YglRGD 
SBH/YglRatfocal segmental glomerulosclerosis  IAGP compared to SBN/YglRGD 
SBN/YglRatfocal segmental glomerulosclerosis sexual_dimorphism IAGPunilateral nephrectomyin males and compared to SBN/Ygl controlRGD 
SBH/YglRathypertension inducedIAGPcontrolled sodium content dietin males more ...RGD 
SBH/YglRatproteinuria MODEL: controlIAGP compared to salt-loaded SBH/YglRGD 
SBH/YglRatproteinuria MODEL: inducedIAGPcontrolled sodium content dietin males more ...RGD 
SBH/YglRatproteinuria severityIAGPunilateral nephrectomyin females and compared to SBH/Ygl controlRGD 
SBH/YglRatproteinuria severityIAGP compared to SBN/YglRGD 
SBH/YglRatproteinuria  IAGPunilateral nephrectomycompared to SBH/Ygl controlRGD 
SBN/YglRatproteinuria MODEL: controlIAGPcontrolled sodium content dietcompared to salt-loaded SBH/YglRGD 
SBN/YglRatproteinuria severityIAGPunilateral nephrectomycompared to SBN/Ygl controlRGD 
SBN/YglRatproteinuria  IAGP  RGD 

Phenotype Annotations    Click to see Annotation Detail View

Mammalian Phenotype

Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
SBN-Chr 17SBH/YglRatdecreased circulating creatinine level inducedIAGPunilateral nephrectomycompared to SBH/YglRGD 
SBN-Chr 1SBH/YglRatdecreased circulating creatinine level inducedIAGPunilateral nephrectomycompared to SBH/Ygl and SBN/YglRGD 
SBH-Chr 1SBN/YglRatdecreased systemic arterial systolic blood pressure  IAGP compared to SBH/YglRGD 
SBH-Chr 1SBN/YglRatdecreased urine protein level inducedIAGPunilateral nephrectomycompared to SBH/YglRGD 
SBH/YglRatglomerulonephritis severityIAGPunilateral nephrectomycompared to uninephrectomized SBN/YglRGD 
SBH/YglRatglomerulonephritis  IAGP compared to SBN/YglRGD 
SBN/YglRatglomerulonephritis sexual_dimorphism IAGPunilateral nephrectomyin males and compared to SBN/Ygl controlRGD 
SBH-Chr 1SBN/YglRatglomerulosclerosis penetranceIAGP compared to SBH/Ygl and SBN/YglRGD 
SBH-Chr 1SBN/YglRatincreased circulating creatinine level inducedIAGPunilateral nephrectomycompared to SBN/YglRGD 
SBH/YglRatincreased circulating creatinine level sexual_dimorphismIAGPunilateral nephrectomyin males more ...RGD 
SBH/YglRatincreased circulating creatinine level sexual_dimorphismIAGP in males and compared to SBN/YglRGD 
SBH/YglRatincreased systemic arterial systolic blood pressure inducedIAGPcontrolled sodium content dietin males more ...RGD 
SBH/YglRatincreased urine protein level severityIAGPunilateral nephrectomyin females and compared to SBH/Ygl controlRGD 
SBH/YglRatincreased urine protein level severityIAGP compared to SBN/YglRGD 
SBH/YglRatincreased urine protein level  IAGPunilateral nephrectomycompared to SBH/Ygl controlRGD 
SBN-Chr 17SBH/YglRatincreased urine protein level disease_progressionIAGP compared to SBN/YglRGD 
SBN-Chr 1SBH/YglRatincreased urine protein level disease_progressionIAGPunilateral nephrectomycompared to SBN/YglRGD 
SBN/YglRatincreased urine protein level severityIAGPunilateral nephrectomycompared to SBN/Ygl controlRGD 
SBN/YglRatincreased urine protein level  IAGP  RGD 
SBH/YglRatsalt-sensitive hypertension inducedIAGPcontrolled sodium content dietin males and compared to SBN/YglRGD 
Objects Annotated

Strains
SBH-Chr 1SBN/Ygl  (NA)
SBH/Ygl  (Sabra hypertension prone)
SBN-Chr 17SBH/Ygl  (NA)
SBN-Chr 1SBH/Ygl  (NA)
SBN/Ygl  (Sabra hypertension resistant)


Additional Information