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

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
LeprRatDiabetic Nephropathies  IAGP DNA:mutations:cds: : (rat)RGD 
ZSF1-Leprfa/cp/CrlRatDiabetic Nephropathies  IAGP compared to lean ZSF1-Leprlean/Crl (RS:0005317)RGD 
LEPRHumanDiastolic Dysfunction  ISOLepr (Rattus norvegicus)DNA:mutations:cds: : (rat)RGD 
LeprRatDiastolic Dysfunction  IAGP DNA:mutations:cds: : (rat)RGD 
LeprMouseDiastolic Dysfunction  ISOLepr (Rattus norvegicus)DNA:mutations:cds: : (rat)RGD 
ZSF1-Leprfa/cp/CrlRatDiastolic Dysfunction  IAGP compared to lean ZSF1-Leprlean/Crl (RS:0005317)RGD 
LEPRHumanMetabolic Syndrome  ISOLepr (Rattus norvegicus)DNA:mutations:cds: : (rat)RGD 
LeprRatMetabolic Syndrome  IAGP DNA:mutations:cds: : (rat)RGD 
LeprMouseMetabolic Syndrome  ISOLepr (Rattus norvegicus)DNA:mutations:cds: : (rat)RGD 
ZSF1-Leprfa/cp/CrlRatMetabolic Syndrome MODEL: spontaneousIAGP compared to lean littermates ZSF1-Leprlean/Crl (RS:0005317)RGD 
ZSF1-Leprlean/CrlRatMetabolic Syndrome MODEL: controlIAGP compared to ZSF1-Leprfa/cp/Crl (RS:0005316)RGD 
COL1A1Humanobesity  ISOCol1a1 (Rattus norvegicus)mRNA:increased expression:kidney (rat)RGD 
COL3A1Humanobesity  ISOCol3a1 (Rattus norvegicus)mRNA:increased expression:kidney (rat)RGD 
COL4A1Humanobesity  ISOCol4a1 (Rattus norvegicus)mRNA:increased expression:kidney (rat)RGD 
Col1a1Ratobesity  IEP mRNA:increased expression:kidney (rat)RGD 
Col1a1Mouseobesity  ISOCol1a1 (Rattus norvegicus)mRNA:increased expression:kidney (rat)RGD 
Col3a1Ratobesity  IEP mRNA:increased expression:kidney (rat)RGD 
Col3a1Mouseobesity  ISOCol3a1 (Rattus norvegicus)mRNA:increased expression:kidney (rat)RGD 
Col4a1Ratobesity  IEP mRNA:increased expression:kidney (rat)RGD 
Col4a1Mouseobesity  ISOCol4a1 (Rattus norvegicus)mRNA:increased expression:kidney (rat)RGD 
LEPRHumanobesity  ISOLepr (Rattus norvegicus)DNA:mutations:cds: : (rat)RGD 
LeprRatobesity  IAGP DNA:mutations:cds: : (rat)RGD 
LeprMouseobesity  ISOLepr (Rattus norvegicus)DNA:mutations:cds: : (rat)RGD 
ZSF1-Leprfa/cp/CrlRatobesity MODEL: spontaneousIAGP compared to lean littermates ZSF1-Leprlean/Crl (RS:0005317)RGD 
ZSF1-Leprlean/CrlRatobesity MODEL: controlIAGP compared to ZSF1-Leprfa/cp/Crl (RS:0005316)RGD 

Phenotype Annotations    Click to see Annotation Detail View

Mammalian Phenotype

Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
LeprRatglomerulosclerosis  IAGP DNA:mutations:cds: : ratRGD 
ZSF1-Leprfa/cp/CrlRatglomerulosclerosis  IAGP compared to lean ZSF1-Leprlean/Crl RS:0005317RGD 
LeprRatincreased blood urea nitrogen level  IAGP DNA:mutations:cds: : ratRGD 
ZSF1-Leprfa/cp/CrlRatincreased blood urea nitrogen level  IAGP compared to lean ZSF1-Leprlean/Crl RS:0005317RGD 
LeprRatincreased circulating cholesterol level  IAGP DNA:mutations:cds: : ratRGD 
ZSF1-Leprfa/cp/CrlRatincreased circulating cholesterol level  IAGP compared to lean ZSF1-Leprlean/Crl RS:0005317RGD 
LeprRatincreased circulating glucose level  IAGP DNA:mutations:cds: : ratRGD 
ZSF1-Leprfa/cp/CrlRatincreased circulating glucose level  IAGP compared to lean ZSF1-Leprlean/Crl RS:0005317RGD 
LeprRatincreased circulating insulin level  IAGP DNA:mutations:cds: : ratRGD 
ZSF1-Leprfa/cp/CrlRatincreased circulating insulin level  IAGP compared to lean ZSF1-Leprlean/Crl RS:0005317RGD 
LeprRatincreased triglyceride level  IAGP DNA:mutations:cds: : ratRGD 
ZSF1-Leprfa/cp/CrlRatincreased triglyceride level  IAGP compared to lean ZSF1-Leprlean/Crl RS:0005317RGD 
LeprRatincreased urine microalbumin level  IAGP DNA:mutations:cds: : ratRGD 
ZSF1-Leprfa/cp/CrlRatincreased urine microalbumin level  IAGP compared to lean ZSF1-Leprlean/Crl RS:0005317RGD 
LeprRatobese  IAGP DNA:mutations:cds: : ratRGD 
ZSF1-Leprfa/cp/CrlRatobese  IAGP compared to lean ZSF1-Leprlean/Crl RS:0005317RGD 
LeprRatrenal cast  IAGP DNA:mutations:cds: : ratRGD 
ZSF1-Leprfa/cp/CrlRatrenal cast  IAGP compared 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