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.



Disease Annotations    
chronic kidney disease  (IMP,ISO)
glucose intolerance  (IMP,ISO)
hypertension  (IAGP,IMP,ISO)
obesity  (IMP,ISO)
proteinuria  (IMP,ISO)
renal fibrosis  (IMP,ISO)

Phenotype Annotations    

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