RGD Reference Report - Creation and characterization of a renin knockout rat. - Rat Genome Database

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Creation and characterization of a renin knockout rat.

Authors: Moreno, C  Hoffman, M  Stodola, TJ  Didier, DN  Lazar, J  Geurts, AM  North, PE  Jacob, HJ  Greene, AS 
Citation: Moreno C, etal., Hypertension. 2011 Mar;57(3):614-9. doi: 10.1161/HYPERTENSIONAHA.110.163840. Epub 2011 Jan 17.
RGD ID: 7771614
Pubmed: PMID:21242461   (View Abstract at PubMed)
PMCID: PMC3513323   (View Article at PubMed Central)
DOI: DOI:10.1161/HYPERTENSIONAHA.110.163840   (Journal Full-text)

The renin-angiotensin system plays an important role in the control of blood pressure (BP) and renal function. To illuminate the importance of renin in the context of a disease background in vivo, we used zinc-finger nucleases (ZFNs) designed to target the renin gene and create a renin knockout in the SS/JrHsdMcwi (SS) rat. ZFN against renin caused a 10-bp deletion in exon 5, resulting in a frameshift mutation. Plasma renin activity was undetectable in the Ren-/- rat, and renin protein was absent from the juxtaglomerular cells in the kidney. Body weight was lower in the Ren-/- rats (than in the Ren+/- or wild-type littermates), and conscious BP on low-salt diet (0.4% NaCl) was 58 +/- 2 mm Hg in the Ren-/- male rats versus 117 mm Hg in the Ren+/- littermates, a reduction of almost 50 mm Hg. Blood urea nitrogen (BUN) and plasma creatinine levels were elevated in the Ren-/- strain (BUN 112 +/- 7 versus 23 +/- 2 mg/dL and creatinine 0.53 +/- 0.02 versus 0.26 +/- 0.02 mg/dL), and kidney morphology was abnormal with a rudimentary inner renal medulla, cortical interstitial fibrosis, thickening of arterial walls, and abnormally shaped glomeruli. The development of the first rat knockout in the renin-angiotensin system demonstrates the efficacy of the ZFN technology for creating knockout rats for cardiovascular disease on any genetic background and emphasizes the role of renin in BP regulation and kidney function even in the low-renin SS rat.



Phenotype Annotations    Click to see Annotation Detail View

Mammalian Phenotype

Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
RenRatabnormal kidney morphology exacerbatesIMP compared to wild typeRGD 
Renem1McwiRatabnormal kidney morphology exacerbatesIMP compared to wild typeRGD 
SS-Renem1Mcwi+/-Ratabnormal kidney morphology exacerbatesIMP compared to wild typeRGD 
SS-Renem1Mcwi-/-Ratabnormal kidney morphology exacerbatesIMP compared to wild typeRGD 
RenRatdecreased body weight  IMP compared to wild typeRGD 
Renem1McwiRatdecreased body weight  IMP compared to wild typeRGD 
SS-Renem1Mcwi-/-Ratdecreased body weight  IMP compared to wild typeRGD 
RenRatdecreased circulating bicarbonate level  IMP compared to wild typeRGD 
Renem1McwiRatdecreased circulating bicarbonate level  IMP compared to wild typeRGD 
SS-Renem1Mcwi-/-Ratdecreased circulating bicarbonate level  IMP compared to wild typeRGD 
RenRatdecreased creatinine clearance  IMP compared to wild typeRGD 
Renem1McwiRatdecreased creatinine clearance  IMP compared to wild typeRGD 
SS-Renem1Mcwi-/-Ratdecreased creatinine clearance  IMP compared to wild typeRGD 
RenRatdecreased mean systemic arterial blood pressure sexual_dimorphismIMP compared to wild type maleRGD 
RenRatdecreased mean systemic arterial blood pressure  IMP compared to wild typeRGD 
Renem1McwiRatdecreased mean systemic arterial blood pressure sexual_dimorphismIMP compared to wild type maleRGD 
Renem1McwiRatdecreased mean systemic arterial blood pressure  IMP compared to wild typeRGD 
SS-Renem1Mcwi+/-Ratdecreased mean systemic arterial blood pressure sexual_dimorphismIMP compared to wild type maleRGD 
SS-Renem1Mcwi-/-Ratdecreased mean systemic arterial blood pressure  IMP compared to wild typeRGD 
RenRatdecreased systemic arterial diastolic blood pressure sexual_dimorphismIMP compared to wild type maleRGD 
RenRatdecreased systemic arterial diastolic blood pressure  IMP compared to wild typeRGD 
Renem1McwiRatdecreased systemic arterial diastolic blood pressure sexual_dimorphismIMP compared to wild type maleRGD 
Renem1McwiRatdecreased systemic arterial diastolic blood pressure  IMP compared to wild typeRGD 
SS-Renem1Mcwi+/-Ratdecreased systemic arterial diastolic blood pressure sexual_dimorphismIMP compared to wild type maleRGD 
SS-Renem1Mcwi-/-Ratdecreased systemic arterial diastolic blood pressure  IMP compared to wild typeRGD 
RenRatdecreased systemic arterial systolic blood pressure sexual_dimorphismIMP compared to wild type maleRGD 
RenRatdecreased systemic arterial systolic blood pressure  IMP compared to wild typeRGD 
Renem1McwiRatdecreased systemic arterial systolic blood pressure sexual_dimorphismIMP compared to wild type maleRGD 
Renem1McwiRatdecreased systemic arterial systolic blood pressure  IMP compared to wild typeRGD 
SS-Renem1Mcwi+/-Ratdecreased systemic arterial systolic blood pressure sexual_dimorphismIMP compared to wild type maleRGD 
SS-Renem1Mcwi-/-Ratdecreased systemic arterial systolic blood pressure  IMP compared to wild typeRGD 
RenRatdecreased urine creatinine level  IMP compared to wild typeRGD 
Renem1McwiRatdecreased urine creatinine level  IMP compared to wild typeRGD 
SS-Renem1Mcwi-/-Ratdecreased urine creatinine level  IMP compared to wild typeRGD 
RenRatdecreased urine protein level  IMP compared to wild typeRGD 
Renem1McwiRatdecreased urine protein level  IMP compared to wild typeRGD 
SS-Renem1Mcwi-/-Ratdecreased urine protein level  IMP compared to wild typeRGD 
RenRatincreased blood urea nitrogen level  IMP  RGD 
Renem1McwiRatincreased blood urea nitrogen level  IMP  RGD 
SS-Renem1Mcwi-/-Ratincreased blood urea nitrogen level  IMP  RGD 
RenRatincreased circulating alanine transaminase level  IMP compared to wild typeRGD 
Renem1McwiRatincreased circulating alanine transaminase level  IMP compared to wild typeRGD 
SS-Renem1Mcwi-/-Ratincreased circulating alanine transaminase level  IMP compared to wild typeRGD 
RenRatincreased circulating creatinine level  IMP compared to wild typeRGD 
Renem1McwiRatincreased circulating creatinine level  IMP compared to wild typeRGD 
SS-Renem1Mcwi-/-Ratincreased circulating creatinine level  IMP compared to wild typeRGD 
RenRatincreased heart rate  IMP compared to wild typeRGD 
Renem1McwiRatincreased heart rate  IMP compared to wild typeRGD 
SS-Renem1Mcwi-/-Ratincreased heart rate  IMP compared to wild typeRGD 
RenRatincreased urine flow rate  IMP compared to wild typeRGD 
Renem1McwiRatincreased urine flow rate  IMP compared to wild typeRGD 
SS-Renem1Mcwi-/-Ratincreased urine flow rate  IMP compared to wild typeRGD 

Objects Annotated

Genes (Rattus norvegicus)
Ren  (renin)
Renem1Mcwi  (renin; zinc finger nuclease induced mutant 1, Medical College of Wisconsin)

Strains
SS-Renem1Mcwi+/-  (SS-Renem1Mcwi+/Renem1Mcwi-)
SS-Renem1Mcwi-/-  (SS-Renem1Mcwi-/Renem1Mcwi-)


Additional Information