RGD Reference Report - A genetic locus on MWF rat chromosome 6 affects kidney damage in response to L-NAME treatment in spontaneously hypertensive rats. - Rat Genome Database

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A genetic locus on MWF rat chromosome 6 affects kidney damage in response to L-NAME treatment in spontaneously hypertensive rats.

Authors: Schulz, A  Schuetten, S  Schulte, L  Kossmehl, P  Nyengaard, JR  Vetter, R  Huber, M  Kreutz, R 
Citation: Schulz A, etal., Physiol Genomics. 2010 Apr 13.
RGD ID: 2317887
Pubmed: PMID:20388842   (View Abstract at PubMed)
DOI: DOI:10.1152/physiolgenomics.00036.2010   (Journal Full-text)

A major quantitative trait loci (QTL) on rat chromosome (RNO)6 was linked to albuminuria in Munich Wistar Fromter (MWF) rats. We tested whether transfer of MWF-RNO6 into the background of albuminuria resistant spontaneously hypertensive rats (SHR) induces albuminuria in consomic SHR-6(MWF) animals. Male MWF, SHR, and SHR-6(MWF) were sham operated and treated between 6 and 24 weeks of age with normal water (Sham) or with water containing 20 mg/l NG-nitro-L-arginine methyl ester (L-NAME) or unilaterally nephrectomized (Nx). Compared to SHR albuminuria was not increased in SHR-6(MWF) in both Sham and Nx. All animals survived the observation period in Sham and Nx, while premature mortality occurred from 12-14 weeks on in L-NAME treated SHR and SHR-6(MWF) compared to MWF L-NAME in which survival was not affected (p<0.005, respectively). Subsequent further analysis of L-NAME treated animals at 12 weeks of age showed significantly increased arterial blood pressures in both SHR and SHR-6(MWF) compared to control (p<0.05) with higher levels in SHR compared to consomics (p<0.05). However, L-NAME treated consomic animals demonstrated increased albuminuria compared to SHR (12.7+/-3.5 vs. 0.8+/-0.2 mg/24h, p<0.05), and an induction of tubulo-interstitial structural injury and expression of neutrophil gelatinase-associated lipocalin mRNA (p<0.05 vs. other strains). Our study demonstrates that the isolation of the RNO6 albuminuria QTL from the MWF background and transfer into SHR fails to induce an albuminuria phenotype during normal conditions or after nephron reduction. Moreover, our date indicate that genes on RNO6 contribute to the development of L-NAME-induced renal damage in the SHR strain.



RGD Manual Disease Annotations    Click to see Annotation Detail View

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
SHR-Chr 6MWF/RkbRatChronic Tubulointerstitial Nephropathy  IAGP compared to SHR/FubRkb and MWF/FubRkbRGD 
SHR-Chr 6MWF/RkbRathypertension  IAGP compared to MWF/FubRkbRGD 

Phenotype Annotations    Click to see Annotation Detail View

Mammalian Phenotype

Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
MWF/FubRkbRatalbuminuria  IAGP compared to SHR/FubRkb and SHR-Chr 6MWF/RkbRGD 
SHR-Chr 6MWF/RkbRatincreased heart left ventricle weight  IAGP compared to MWF/FubRkbRGD 
SHR-Chr 6MWF/RkbRatincreased mean systemic arterial blood pressure  IAGP compared to MWF/FubRkbRGD 
SHR-Chr 6MWF/RkbRatincreased systemic arterial systolic blood pressure inducedIAGPNG-nitroarginine methyl estercompared to SHR/FubRkbRGD 
SHR-Chr 6MWF/RkbRatincreased systemic arterial systolic blood pressure  IAGP compared to MWF/FubRkbRGD 

Objects Annotated

Strains
MWF/FubRkb  (Munich Wistar Fromter)
SHR-Chr 6MWF/Rkb  (NA)


Additional Information