RGD Reference Report - Early development of podocyte injury independently of hyperglycemia and elevations in arterial pressure in nondiabetic obese Dahl SS leptin receptor mutant rats. - Rat Genome Database

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Early development of podocyte injury independently of hyperglycemia and elevations in arterial pressure in nondiabetic obese Dahl SS leptin receptor mutant rats.

Authors: McPherson, Kasi C  Taylor, Lateia  Johnson, Ashley C  Didion, Sean P  Geurts, Aron M  Garrett, Michael R  Williams, Jan M 
Citation: McPherson KC, etal., Am J Physiol Renal Physiol. 2016 Oct 1;311(4):F793-F804. doi: 10.1152/ajprenal.00590.2015. Epub 2016 Jul 27.
RGD ID: 12911217
Pubmed: PMID:27465994   (View Abstract at PubMed)
PMCID: PMC5142236   (View Article at PubMed Central)
DOI: DOI:10.1152/ajprenal.00590.2015   (Journal Full-text)

The current study examined the effect of obesity on the development of renal injury within the genetic background of the Dahl salt-sensitive rat with a dysfunctional leptin receptor derived from zinc-finger nucleases (SS(LepR)mutant strain). At 6 wk of age, body weight was 35% higher in the SS(LepR)mutant strain compared with SSWT rats and remained elevated throughout the entire study. The SS(LepR)mutant strain exhibited impaired glucose tolerance and increased plasma insulin levels at 6 wk of age, suggesting insulin resistance while SSWT rats did not. However, blood glucose levels were normal throughout the course of the study. Systolic arterial pressure (SAP) was similar between the two strains from 6 to 10 wk of age. However, by 18 wk of age, the development of hypertension was more severe in the SS(LepR)mutant strain compared with SSWT rats (201 ± 10 vs. 155 ± 3 mmHg, respectively). Interestingly, proteinuria was substantially higher at 6 wk of age in the SS(LepR)mutant strain vs. SSWT rats (241 ± 27 vs. 24 ± 2 mg/day, respectively) and remained elevated until the end of the study. The kidneys from the SS(LepR)mutant strain displayed significant glomerular injury, including podocyte foot process effacement and lipid droplets compared with SSWT rats as early as 6 wk of age. By 18 wk of age, plasma creatinine levels were twofold higher in the SS(LepR)mutant strain vs. SSWT rats, suggesting the presence of chronic kidney disease (CKD). Overall, these results indicate that the SS(LepR)mutant strain develops podocyte injury and proteinuria independently of hyperglycemia and elevated arterial pressure that later progresses to CKD.



RGD Manual Disease Annotations    Click to see Annotation Detail View

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
LEPRHumanchronic kidney disease  ISORGD:3001 RGD 
LeprRatchronic kidney disease  IMP  RGD 
LeprMousechronic kidney disease  ISORGD:3001 RGD 
Leprem2McwiRatchronic kidney disease  IMP  RGD 
SS-Leprem2McwiRatchronic kidney disease MODEL: spontaneousIMP  RGD 
LEPRHumanglucose intolerance  ISORGD:3001 RGD 
LeprRatglucose intolerance  IMP  RGD 
LeprMouseglucose intolerance  ISORGD:3001 RGD 
Leprem2McwiRatglucose intolerance  IMP  RGD 
LEPRHumanhypertension disease_progressionISORGD:3001 RGD 
LeprRathypertension disease_progressionIMP  RGD 
LeprMousehypertension disease_progressionISORGD:3001 RGD 
Leprem2McwiRathypertension disease_progressionIMP  RGD 
SS-Leprem2McwiRathypertension disease_progressionIMP  RGD 
SS/JrHsdMcwiRathypertension  IAGP  RGD 
LEPRHumanobesity  ISORGD:3001 RGD 
LEPRHumanobesity disease_progressionISORGD:3001 RGD 
LeprRatobesity disease_progressionIMP  RGD 
LeprRatobesity  IMP  RGD 
LeprMouseobesity disease_progressionISORGD:3001 RGD 
LeprMouseobesity  ISORGD:3001 RGD 
Leprem2McwiRatobesity  IMP  RGD 
Leprem2McwiRatobesity disease_progressionIMP  RGD 
SS-Leprem2McwiRatobesity disease_progressionIMP  RGD 
LEPRHumanproteinuria  ISORGD:3001compared to SS/JrHsdMcwiRGD 
LeprRatproteinuria  IMP compared to SS/JrHsdMcwiRGD 
LeprMouseproteinuria  ISORGD:3001compared to SS/JrHsdMcwiRGD 
Leprem2McwiRatproteinuria  IMP compared to SS/JrHsdMcwiRGD 
SS-Leprem2McwiRatproteinuria  IMP compared to SS/JrHsdMcwiRGD 
LEPRHumanrenal fibrosis disease_progressionISORGD:3001 RGD 
LeprRatrenal fibrosis disease_progressionIMP  RGD 
LeprMouserenal fibrosis disease_progressionISORGD:3001 RGD 
Leprem2McwiRatrenal fibrosis disease_progressionIMP  RGD 
SS-Leprem2McwiRatrenal fibrosis disease_progressionIMP  RGD 

Phenotype Annotations    Click to see Annotation Detail View

Mammalian Phenotype

Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
LeprRatabnormal glomerular filtration barrier morphology  IMP  RGD 
Leprem2McwiRatabnormal glomerular filtration barrier morphology  IMP  RGD 
SS-Leprem2McwiRatabnormal glomerular filtration barrier morphology  IMP compared to SS/JrHsdMcwiRGD 
LeprRatglomerulosclerosis disease_progressionIMP  RGD 
Leprem2McwiRatglomerulosclerosis disease_progressionIMP  RGD 
SS-Leprem2McwiRatglomerulosclerosis disease_progressionIMP  RGD 
LeprRathypertension  IMP  RGD 
LeprRatimpaired glucose tolerance  IMP compared to SS/JrHsdMcwiRGD 
Leprem2McwiRatimpaired glucose tolerance  IMP compared to SS/JrHsdMcwiRGD 
SS-Leprem2McwiRatimpaired glucose tolerance  IMP compared to SS/JrHsdMcwiRGD 
LeprRatincreased body weight  IMP  RGD 
Leprem2McwiRatincreased body weight  IMP  RGD 
SS-Leprem2McwiRatincreased body weight  IMP compared to SS/JrHsdMcwiRGD 
LeprRatincreased circulating cholesterol level disease_progressionIMP  RGD 
Leprem2McwiRatincreased circulating cholesterol level disease_progressionIMP  RGD 
SS-Leprem2McwiRatincreased circulating cholesterol level disease_progressionIMP  RGD 
LeprRatincreased circulating creatinine level  IMP  RGD 
Leprem2McwiRatincreased circulating creatinine level  IMP  RGD 
SS-Leprem2McwiRatincreased circulating creatinine level  IMP compared to SS/JrHsdMcwiRGD 
LeprRatincreased circulating insulin level  IMP  RGD 
Leprem2McwiRatincreased circulating insulin level  IMP  RGD 
SS-Leprem2McwiRatincreased circulating insulin level  IMP compared to SS/JrHsdMcwiRGD 
LeprRatincreased circulating leptin level  IMP  RGD 
Leprem2McwiRatincreased circulating leptin level  IMP  RGD 
SS-Leprem2McwiRatincreased circulating leptin level  IMP compared to SS/JrHsdMcwiRGD 
LeprRatincreased circulating triglyceride level disease_progressionIMP  RGD 
Leprem2McwiRatincreased circulating triglyceride level disease_progressionIMP  RGD 
SS-Leprem2McwiRatincreased circulating triglyceride level disease_progressionIMP  RGD 
LeprRatincreased systemic arterial systolic blood pressure onsetIMP compared to SS/JrHsdMcwiRGD 
Leprem2McwiRatincreased systemic arterial systolic blood pressure onsetIMP compared to SS/JrHsdMcwiRGD 
SS-Leprem2McwiRatincreased systemic arterial systolic blood pressure onsetIMP compared to SS/JrHsdMcwiRGD 
LeprRatincreased urine protein level  IMP  RGD 
Leprem2McwiRatincreased urine protein level  IMP  RGD 
SS-Leprem2McwiRatincreased urine protein level  IMP compared to SS/JrHsdMcwiRGD 
LeprRatinsulin resistance  IMP  RGD 
Leprem2McwiRatinsulin resistance  IMP  RGD 
LeprRatpodocyte foot process effacement  IMP  RGD 
Leprem2McwiRatpodocyte foot process effacement  IMP  RGD 
SS-Leprem2McwiRatpodocyte foot process effacement  IMP  RGD 
LeprRatrenal interstitial fibrosis disease_progressionIMP compared to SS/JrHsdMcwiRGD 
Leprem2McwiRatrenal interstitial fibrosis disease_progressionIMP compared to SS/JrHsdMcwiRGD 
SS-Leprem2McwiRatrenal interstitial fibrosis disease_progressionIMP compared to SS/JrHsdMcwiRGD 

Objects Annotated

Genes (Rattus norvegicus)
Lepr  (leptin receptor)
Leprem2Mcwi  (leptin receptor; zinc finger nuclease induced mutant 2, Medical College of Wisconsin)

Genes (Mus musculus)
Lepr  (leptin receptor)

Genes (Homo sapiens)
LEPR  (leptin receptor)

Strains
SS-Leprem2Mcwi  (NA)
SS/JrHsdMcwi  (NA)


Additional Information