RGD Reference Report - High resolution molecular and histological analysis of renal disease progression in ZSF1 fa/faCP rats, a model of type 2 diabetic nephropathy. - Rat Genome Database

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High resolution molecular and histological analysis of renal disease progression in ZSF1 fa/faCP rats, a model of type 2 diabetic nephropathy.

Authors: Dower, Ken  Zhao, Shanrong  Schlerman, Franklin J  Savary, Leigh  Campanholle, Gabriela  Johnson, Bryce G  Xi, Li  Nguyen, Vuong  Zhan, Yutian  Lech, Matthew P  Wang, Ju  Nie, Qing  Karsdal, Morten A  Genovese, Federica  Boucher, Germaine  Brown, Thomas P  Zhang, Baohong  Homer, Bruce L  Martinez, Robert V 
Citation: Dower K, etal., PLoS One. 2017 Jul 26;12(7):e0181861. doi: 10.1371/journal.pone.0181861. eCollection 2017.
RGD ID: 401965413
Pubmed: PMID:28746409   (View Abstract at PubMed)
PMCID: PMC5529026   (View Article at PubMed Central)
DOI: DOI:10.1371/journal.pone.0181861   (Journal Full-text)

ZSF1 rats exhibit spontaneous nephropathy secondary to obesity, hypertension, and diabetes, and have gained interest as a model system with potentially high translational value to progressive human disease. To thoroughly characterize this model, and to better understand how closely it recapitulates human disease, we performed a high resolution longitudinal analysis of renal disease progression in ZSF1 rats spanning from early disease to end stage renal disease. Analyses included metabolic endpoints, renal histology and ultrastructure, evaluation of a urinary biomarker of fibrosis, and transcriptome analysis of glomerular-enriched tissue over the course of disease. Our findings support the translational value of the ZSF1 rat model, and are provided here to assist researchers in the determination of the model's suitability for testing a particular mechanism of interest, the design of therapeutic intervention studies, and the identification of new targets and biomarkers for type 2 diabetic nephropathy.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
Diabetic Nephropathies  IAGP 401965413DNA:mutations:cds: : (rat)RGD 
Diabetic Nephropathies  IAGP 401965413compared to lean ZSF1-Leprlean/Crl (RS:0005317)RGD 
Diastolic Dysfunction  ISOLepr (Rattus norvegicus)401965413; 401965413DNA:mutations:cds: : (rat)RGD 
Diastolic Dysfunction  IAGP 401965413DNA:mutations:cds: : (rat)RGD 
Diastolic Dysfunction  IAGP 401965413compared to lean ZSF1-Leprlean/Crl (RS:0005317)RGD 
Metabolic Syndrome  ISOLepr (Rattus norvegicus)401965413; 401965413DNA:mutations:cds: : (rat)RGD 
Metabolic Syndrome  IAGP 401965413DNA:mutations:cds: : (rat)RGD 
Metabolic Syndrome MODEL: spontaneousIAGP 401965413compared to lean littermates ZSF1-Leprlean/Crl (RS:0005317)RGD 
Metabolic Syndrome MODEL: controlIAGP 401965413compared to ZSF1-Leprfa/cp/Crl (RS:0005316)RGD 
obesity  ISOCol1a1 (Rattus norvegicus)401965413; 401965413mRNA:increased expression:kidney (rat)RGD 
obesity  ISOCol3a1 (Rattus norvegicus)401965413; 401965413mRNA:increased expression:kidney (rat)RGD 
obesity  ISOCol4a1 (Rattus norvegicus)401965413; 401965413mRNA:increased expression:kidney (rat)RGD 
obesity  IEP 401965413; 401965413; 401965413mRNA:increased expression:kidney (rat)RGD 
obesity  ISOLepr (Rattus norvegicus)401965413; 401965413DNA:mutations:cds: : (rat)RGD 
obesity  IAGP 401965413DNA:mutations:cds: : (rat)RGD 
obesity MODEL: spontaneousIAGP 401965413compared to lean littermates ZSF1-Leprlean/Crl (RS:0005317)RGD 
obesity MODEL: controlIAGP 401965413compared to ZSF1-Leprfa/cp/Crl (RS:0005316)RGD 

Phenotype Annotations    Click to see Annotation Detail View

Mammalian Phenotype

TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
glomerulosclerosis  IAGP 401965413DNA:mutations:cds: : ratRGD 
glomerulosclerosis  IAGP 401965413compared to lean ZSF1-Leprlean/Crl RS:0005317RGD 
increased blood urea nitrogen level  IAGP 401965413DNA:mutations:cds: : ratRGD 
increased blood urea nitrogen level  IAGP 401965413compared to lean ZSF1-Leprlean/Crl RS:0005317RGD 
increased circulating cholesterol level  IAGP 401965413DNA:mutations:cds: : ratRGD 
increased circulating cholesterol level  IAGP 401965413compared to lean ZSF1-Leprlean/Crl RS:0005317RGD 
increased circulating glucose level  IAGP 401965413DNA:mutations:cds: : ratRGD 
increased circulating glucose level  IAGP 401965413compared to lean ZSF1-Leprlean/Crl RS:0005317RGD 
increased circulating insulin level  IAGP 401965413DNA:mutations:cds: : ratRGD 
increased circulating insulin level  IAGP 401965413compared to lean ZSF1-Leprlean/Crl RS:0005317RGD 
increased triglyceride level  IAGP 401965413DNA:mutations:cds: : ratRGD 
increased triglyceride level  IAGP 401965413compared to lean ZSF1-Leprlean/Crl RS:0005317RGD 
increased urine microalbumin level  IAGP 401965413DNA:mutations:cds: : ratRGD 
increased urine microalbumin level  IAGP 401965413compared to lean ZSF1-Leprlean/Crl RS:0005317RGD 
obese  IAGP 401965413DNA:mutations:cds: : ratRGD 
obese  IAGP 401965413compared to lean ZSF1-Leprlean/Crl RS:0005317RGD 
renal cast  IAGP 401965413DNA:mutations:cds: : ratRGD 
renal cast  IAGP 401965413compared to lean ZSF1-Leprlean/Crl RS:0005317RGD 
Objects Annotated

Genes (Rattus norvegicus)
Col1a1  (collagen type I alpha 1 chain)
Col3a1  (collagen type III alpha 1 chain)
Col4a1  (collagen type IV alpha 1 chain)
Lepr  (leptin receptor)

Genes (Mus musculus)
Col1a1  (collagen, type I, alpha 1)
Col3a1  (collagen, type III, alpha 1)
Col4a1  (collagen, type IV, alpha 1)
Lepr  (leptin receptor)

Genes (Homo sapiens)
COL1A1  (collagen type I alpha 1 chain)
COL3A1  (collagen type III alpha 1 chain)
COL4A1  (collagen type IV alpha 1 chain)
LEPR  (leptin receptor)


Additional Information